Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 12/2002

01-10-2002 | Review Article

Ontogeny of Hepatic and Renal Systemic Clearance Pathways in Infants Part I

Authors: Jane Alcorn, Dr Patrick J. McNamara

Published in: Clinical Pharmacokinetics | Issue 12/2002

Login to get access

Abstract

Dramatic developmental changes in the physiological and biochemical processes that govern drug pharmacokinetics and pharmacodynamics occur during the first year of life. These changes may have significant consequences for the way infants respond to and dealwith drugs. The ontogenesis of systemic clearance mechanisms is probably the most critical determinant of a pharmacological response in the developing infant. In recent years, advances in molecular techniques and an increased availability of fetal and infant tissues have afforded enhanced insight into the ontogeny of clearance mechanisms. Information from these studies is reviewed to highlight the dynamic and complex nature of developmental changes in clearance mechanisms in infants during the first year of life.
Hepatic and renal elimination mechanisms constitute the two principal clearance pathways of the developing infant. Drug metabolising enzyme activity is primarily responsible for the hepatic clearance of many drugs. In general, when compared with adult activity levels normalised to amount of hepatic microsomal protein, hepatic cytochrome P450-mediated metabolism and the phase II reactions of glucuronidation, glutathione conjugation and acetylation are deficient in the neonate, but sulfate conjugation is an efficient pathway at birth. Parturition triggers the dramatic development of drug metabolising enzymes, and each enzyme demonstrates an independent rate and pattern of maturation. Marked inter-individual variability is associated with their developmental expression, making the ontogenesis of hepatic metabolism a highly variable process. By the first year of life, most enzymes have matured to adult activity levels.
When compared with adult values, renal clearance mechanisms are compromised at birth. Dramatic increases in renal function occur in the ensuing postpar-tum period, and by 6 months of age glomerular filtration rate normalised to bodyweight has approached adult values. Maturation of renal tubular functions exhibits a more protracted time course of development, resulting in a glomerulotubular imbalance. This imbalance exists until adult renal tubule function values are approached by 1 year of age. The ontogeny of hepatic biliary and renal tubular transport processes and their impact on the elimination of drugs remain largely unknown.
The summary of the current understanding of the ontogeny of individual pathways of hepatic and renal elimination presented in this review should serve as a basis for the continued accruement of age-specific information concerning the ontogeny of clearance mechanisms in infants. Such information can only help to improve the pharmacotherapeutic management of paediatric patients.
Literature
1.
Gilman JT, Gal P. Pharmacokinetic and pharmacodynamic data collection in children and neonates: a quiet frontier [comment]. Clin Pharmacokinet 1992; 23(1): 1–9PubMedCrossRef
2.
Alcorn J, McNamara PJ. Ontogeny of hepatic and renal systemic clearance pathways in infants: part II. Clin Pharmacokinet. In press
3.
4.
5.
6.
7.
8.
Morselli PL, Franco-Morselli R, Bossi L. Clinical pharmacoki-netics in newborns and infants: age-related differences and therapeutic implications. Clin Pharmacokinet 1980; 5(6): 485–527PubMedCrossRef
9.
Morselli PL. Clinical pharmacology of the perinatal period and early infancy. Clin Pharmacokinet 1989; 17 Suppl. 1: 13–28PubMedCrossRef
10.
Stewart CF, Hampton EM. Effect of maturation on drug disposition in pediatric patients. Clin Pharm 1987; 6(7): 548–64PubMed
11.
Warner A. Drug use in the neonate: interrelationships of phar-macokinetics, toxicity, and biochemical maturity. Clin Chem 1986; 32(5): 721–7PubMed
12.
Johnson TN, Tanner MS, Tucker GT. A comparison of the ontogeny of enterocytic and hepatic cytochromes P450 3A in the rat. Biochem Pharmacol 2000; 60(11): 1601–10PubMedCrossRef
13.
Rowland M, Benet LZ, Graham GG. Clearance concepts in pharmacokinetics. J Pharmacokinet Biopharm 1973; 1(2): 123–36PubMed
14.
Pang KS, Rowland M. Hepatic clearance of drugs: I. Theoretical considerations of a well-stirred model and a parallel tube model. Influence of hepatic blood flow, plasma and blood cell binding, and the hepatocellular enzymatic activity on hepatic drag clearance. J Pharmacokinet Biopharm 1977; 5(6): 625–53PubMed
15.
Yamazaki M, Suzuki H, Sugiyama Y. Recent advances in carrier-mediated hepatic uptake and biliary excretion of xenobiotics. PharmRes 1996; 13(4): 497–513
16.
Edelstone DI, Rudolph AM, Heymann MA. Liver and ductus venosus blood flows in fetal lambs in utero. Circ Res 1978; 42(3): 426–33PubMedCrossRef
17.
Ring JA, Ghabrial H, Ching MS, et al. Fetal hepatic drug elimination. Pharmacol Ther 1999; 84(3): 429–45PubMedCrossRef
18.
Rudolph AM. Hepatic and ductus venosus blood flows during fetal life. Hepatology 1983; 3(2): 254–8PubMedCrossRef
19.
20.
Fahey JT. Developmental aspects of hepatic blood flow. In: Suchy FJ, editor. Liver disease in children. St Louis: Mosby-YearBooklnc, 1994: 31–8
21.
Holzman IR. Fetal and neonatal hepatic perfusion and oxygen-ation. Semin Perinatol 1984; 8(3): 234–44PubMed
22.
Oude Elferink RP, Meijer DK, Kuipers F, et al. Hepatobiliary secretion of organic compounds; molecular mechanisms of membrane transport. Biochim Biophys Acta 1995; 1241(2): 215–68PubMedCrossRef
23.
Meier PJ. Hepatocellular transport systems: from carrier identification in membrane vesicles to cloned proteins. J Hepatol 1996; 24 Suppl. 1: 29–35PubMed
24.
Wolkoff AW, Suchy FJ, Moseley RH, et al. Advances in hepatic transport: molecular mechanisms, genetic disorders, and treatment. A summary of the 1998 AASLD single topic conference. Hepatology 1998; 28(6): 1713–9PubMedCrossRef
25.
Balistreri WF. Immaturity of hepatic excretory function and the ontogeny of bile acid metabolism. J Pediatr Gastroenterol Nutr 1983; 2 Suppl. 1: S207–14PubMedCrossRef
26.
Goldstein J. Sulfobromophthalein sodium (BSP) conjugation and excretion in neonatal guinea pigs. Am J Physiol 1965; 208: 573–7PubMed
27.
Klaassen CD. Immaturity of the newborn rat’s hepatic excretory function for ouabain. J Pharmacol Exp Ther 1972; 183(3): 520–6PubMed
28.
Hwang SW, Dixon RL. Perinatal development of indocyanine green biliary excretion in guinea pigs. Am J Physiol 1973; 225(6): 1454–9PubMed
29.
Fischer E, Barth A, Varga F, et al. Age dependence of hepatic transport in control and phenobarbital-pretreated rats. Life Sci 1979; 24(6): 557–62PubMedCrossRef
30.
Cagen SZ, Gibson JE. Characteristics of hepatic excretory function during development. J Pharmacol Exp Ther 1979; 210(1): 15–21PubMed
31.
Findlay JW, Butz RF, Sailstad JM, et al. Pseudoephedrine and triprolidine in plasma and breast milk of nursing mothers. Br J Clin Pharmacol 1984; 18(6): 901–6PubMedCrossRef
32.
Stacey NH, Klaassen CD. Uptake of ouabain by isolated hepa-tocytes from livers of developing rats. J Pharmacol Exp Ther 1979; 211(2): 360–3PubMed
33.
Suchy FJ, Balistreri WF. Uptake of taurocholate by hepatocytes isolated from developing rats. Pediatr Res 1982; 16(4 Pt 1): 282–5PubMedCrossRef
34.
Dutt A, Priebe TS, Teeter LD, et al. Postnatal development of organic cation transport and mdr gene expression in mouse kidney. J Pharmacol Exp Ther 1992; 261(3): 1222–30PubMed
35.
Dubuisson C, Cresteil D, Desrochers M, et al. Ontogenic expression of the Na+-independent organic anion transporting polypeptide (oatp) in rat liver and kidney. J Hepatol 1996; 25(6): 932–40PubMedCrossRef
36.
Martel F, Martins MJ, Calhau C, et al. Postnatal development of organic cation transport in the rat liver. Pharmacol Res 1998; 37(2): 131–6PubMedCrossRef
37.
Kojima T, Nishimura M, Yajima T, et al. Developmental changes in the regional Na+/glucose transporter mRNA along the small intestine of suckling rats. Comp Biochem Physiol B Biochem Mol Biol 1999; 122(1): 89–95PubMedCrossRef
38.
Matsuoka Y, Okazaki M, Kitamura Y, et al. Developmental expression of P-glycoprotein (multidrug resistance gene product) in the rat brain. J Neurobiol 1999; 39(3): 383–92PubMedCrossRef
39.
Pavlova A, Sakurai H, Leclercq B, et al. Developmentally regulated expression of organic ion transporters NKT (OAT1), OCT1, NLT (OAT2), and Roct. Am J Physiol Renal Physiol 2000; 278(4): F635–43
40.
van Kalken C, Giaccone G, van der Valk P, et al. Multidrug resistance gene (P-glycoprotein) expression in the human fetus. Am J Pathol 1992; 141(5): 1063–72PubMed
41.
Schumacher U, Mollgard K. The multidrug-resistance P-glycoprotein (Pgp, MDR1) is an early marker of blood-brain barrier development in the microvessels of the developing human brain. Histochem Cell Biol 1997; 108(2): 179–82PubMedCrossRef
42.
Williams RT. Detoxification mechanisms. New York: Wiley and Sons, 1959
43.
Tanaka E, Breimer DD. In vivo function tests of hepatic drag-oxidizing capacity in patients with liver disease. J Clin Pharm Ther 1997; 22(4): 237–49PubMedCrossRef
44.
Rich KJ, Boobis AR. Expression and inducibility of P450 enzymes during liver ontogeny. Microsc Res Tech 1997; 39(5): 424–35PubMedCrossRef
45.
Rowell M, Zlotkin S. The ethical boundaries of drug research in pediatrics. Pediatr Clin North Am 1997; 44(1): 27–40PubMedCrossRef
46.
Crom WR, Webster SL, Bobo L, et al. Simultaneous administration of multiple model substrates to assess hepatic drug clearance. Clin Pharmacol Ther 1987; 41(6): 645–50PubMedCrossRef
47.
Relling MV, Crom WR, Pieper JA, et al. Hepatic drag clearance in children with leukemia: changes in clearance of model substrates during remission-induction therapy. Clin Pharmacol Ther 1987; 41(6): 651–60PubMedCrossRef
48.
Blumer JL. Clinical pharmacology of midazolam in infants and children. Clin Pharmacokinet 1998; 35(1): 37–47PubMedCrossRef
49.
Gorski JC, Hall SD, Jones DR, et al. Regioselective biotrans-formation of midazolam by members of the human cyto-chrome P450 3A (CYP3A) subfamily. Biochem Pharmacol 1994; 47(9): 1643–53PubMedCrossRef
50.
Vauzelle-Kervroedan F, Rey E, Pariente-Khayat A, et al. Non invasive in vivo study of the maturation of CYP IIIA in neo-nates and infants. Eur J Clin Pharmacol 1996; 51(1): 69–72PubMedCrossRef
51.
Nakamura H, Hirai M, Ohmori S, et al. Changes in urinary 6p-hydroxycortisol/cortisol ratio after birth in human neo-nates. Eur J Clin Pharmacol 1998; 53(5): 343–6PubMedCrossRef
52.
Miners JO, Birkett DJ. The use of caffeine as a metabolic probe for human drug metabolizing enzymes. Gen Pharmacol 1996; 27(2): 245–9PubMedCrossRef
53.
Treluyer JM, Cheron G, Sonnier M, et al. Cytochrome P-450 expression in sudden infant death syndrome. Biochem Pharmacol 1996; 52(3): 497–504PubMedCrossRef
54.
Pearce RE, Mclntyre CJ, Madan A, et al. Effects of freezing, thawing, and storing human liver microsomes on cytochrome P450 activity. Arch Biochem Biophys 1996; 331(2): 145–69PubMedCrossRef
55.
Powis G, Jardine I, Van Dyke R, et al. Foreign compound metabolism studies with human liver obtained as surgical waste: relation to donor characteristics and effects of tissue storage. Drug Metab Dispos 1988; 16(4): 582–9PubMed
56.
Yamazaki H, Inoue K, Turvy CG, et al. Effects of freezing, thawing, and storage of human liver samples on the micro-somal contents and activities of cytochrome P450 enzymes. Drug Metab Dispos 1997; 25(2): 168–74PubMed
57.
Schoene B, Fleischmann RA, Remmer H, et al. Determination of drug metabolizing enzymes in needle biopsies of human liver. Eur J Clin Pharmacol 1972; 4(2): 65–73PubMedCrossRef
58.
Jondorf WR, Donahue JD. The post-mortem diminution of rat liver microsomal protein synthesizing and drug metabolizing activities. Res Commun Chem Pathol Pharmacol 1970; 1(5): 581–90PubMed
59.
Walker E, McNicol AM. In situ hybridization demonstrates the stability of mRNA in post-mortem rat tissues. J Pathol 1992; 168(1): 67–73PubMedCrossRef
60.
Macleod SM, Renton KW, Eade NR. Post mortem characteristics of the hepatic microsomal drug oxidising enzyme system. Chem Biol Interact 1973; 7(1): 29–37PubMedCrossRef
61.
Skett P, Tyson C, Guillouzo A, et al. Report on the international workshop on the use of human in vitro liver preparations to study drug metabolism in drug development: 1994 Sep 6–8; Utrecht, The Netherland. Biochem Pharmacol 1995; 50(2): 280–5PubMedCrossRef
62.
Guengerich FP. Analysis and characterization of enzymes. In: Hayes AW, editor. Principles and methods of toxicology. New York: Raven Press, 1994: 1259–313
63.
Guengerich FP, Shimada T. Oxidation of toxic and carcinogenic chemicals by human cytochrome P-450 enzymes. Chem Res Toxicol 1991; 4(4): 391–407PubMedCrossRef
64.
Guengerich FP, Turvy CG. Comparison of levels of several human microsomal cytochrome P-450 enzymes and epoxide hydrolase in normal and disease states using immunochemi-cal analysis of surgical liver samples. J Pharmacol Exp Ther 1991; 256(3): 1189–94PubMed
65.
Shimada T, Yamazaki H, Mimura M, et al. Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 1994; 270(1): 414–23PubMed
66.
Hardman JG, Limbird LE, editors. Goodman and Gilman’s the pharmacological basis of therapeutics. 9th ed. New York: McGraw-Hill, 1996
67.
Treluyer JM, Gueret G, Cheron G, et al. Developmental expression of CYP2C and CYP2C-dependent activities in the human liver: in-vivo/in-vitro correlation and inducibility. Pharmacogenetics 1997; 7(6): 441–52PubMedCrossRef
68.
Shimada T, Yamazaki H, Mimura M, et al. Characterization of microsomal cytochrome P450 enzymes involved in the oxidation of xenobiotic chemicals in human fetal liver and adult lungs. Drug Metab Dispos 1996; 24(5): 515–22PubMed
69.
Yang HY, Namkung MJ, Juchau MR. Expression of functional cytochrome P4501A1 in human embryonic hepatic tissues during organogenesis. Biochem Pharmacol 1995; 49(5): 717–26PubMedCrossRef
70.
Berthou F, Ratanasavanh D, Alix D, et al. Caffeine and theo-phylline metabolism in newborn and adult human hepato-cytes; comparison with adult rat hepatocytes. Biochem Pharmacol 1988; 37(19): 3691–700PubMedCrossRef
71.
Cazeneuve C, Pons G, Rey E, et al. Biotransformation of caffeine in human liver microsomes from foetuses, neonates, infants and adults. Br J Clin Pharmacol 1994; 37(5): 405–12PubMedCrossRef
72.
Hakkola J, Pasanen M, Pelkonen O, et al. Expression of CYP1B1 in human adult and fetal tissues and differential inducibility of CYP IB 1 and CYP1A1 by Ah receptor ligands in human placenta and cultured cells. Carcinogenesis 1997; 18(2): 391–7PubMedCrossRef
73.
Hakkola J, Tanaka E, Pelkonen O. Developmental expression of cytochrome P450 enzymes in human liver. Pharmacol Toxicol 1998; 82(5): 209–17PubMedCrossRef
74.
Pearce R, Greenway D, Parkinson A. Species differences and interindividual variation in liver microsomal cytochrome P450 2A enzymes: effects on coumarin, dicumarol, and testosterone oxidation. Arch Biochem Biophys 1992; 298(1): 211–25PubMedCrossRef
75.
Umbenhauer DR, Martin MV, Lloyd RS, et al. Cloning and sequence determination of a complementary DNA related to human liver microsomal cytochrome P-450 S-mephenytoin 4-hydroxylase. Biochemistry 1987; 26(4): 1094–9PubMedCrossRef
76.
Jacqz-Aigrain E, Cresteil T. Cytochrome P450-dependent metabolism of dextromethorphan: fetal and adult studies. Dev Pharmacol Ther 1992; 18(3–4): 161-8
77.
Treluyer JM, Jacqz-Aigrain E, Alvarez F, et al. Expression of CYP2D6 in developing human liver. Eur J Biochem 1991; 202(2): 583–8PubMedCrossRef
78.
Vieira I, Sonnier M, Cresteil T. Developmental expression of CYP2E1 in the human liver: hypermethylation control of gene expression during the neonatal period. Eur J Biochem 1996; 238(2): 476–83PubMedCrossRef
79.
Lacroix D, Sonnier M, Moncion A, et al. Expression of CYP3A in the human liver: evidence that the shift between CYP3A7 and CYP3A4 occurs immediately after birth. Eur J Biochem 1997; 247(2): 625–34PubMedCrossRef
80.
Keiding S. Galactose clearance measurements and liver blood flow. Gastroenterology 1988; 94(2): 477–81PubMed
81.
Leevy CM, Mendenhall CL, Lesko W, et al. Estimation of hepatic blood flow with indocyanine green. J Clin Invest 1962; 41(5): 1169–79PubMedCrossRef
82.
Evans WE, Relling MV, de Graaf S, et al. Hepatic drug clearance in children: studies with indocyanine green as a model substrate. J Pharm Sci 1989; 78(6): 452–6PubMedCrossRef
83.
Roth B, Statz A, Heinisch HM, et al. Elimination of indocyanine green by the liver of infants with hypertrophic pyloric stenosis and the icteropyloric syndrome. J Pediatr 1981; 99(2): 240–3PubMedCrossRef
84.
Murry DJ, Crom WR, Reddick WE, et al. Liver volume as a determinant of drug clearance in children and adolescents. Drug Metab Dispos 1995; 23(10): 1110–6PubMed
85.
Bradley SE, Ingelfinger FJ, Bradley GP, et al. The estimation of hepatic blood flow in man. J Clin Invest 1945; 24: 890–7CrossRef
86.
Hendeles L, Weinberger M. Theophylline: a state of the art review. Pharmacotherapy 1983; 3(1): 2–44PubMed
87.
Kandrotas RJ, Cranfield TL, Gal P, et al. Effect of phenobarbi-tal administration on theophylline clearance in premature neonates. Ther Drug Monit 1990; 12(2): 139–43PubMedCrossRef
88.
Moore ES, Faix RG, Banagale RC, et al. The population phar-macokinetics of theophylline in neonates and young infants. J Pharmacokinet Biopharm 1989; 17(1): 47–66PubMed
89.
Anderson BJ, Holford NH, Woollard GA. Aspects of theophylline clearance in children. Anaesth Intensive Care 1997; 25(5): 497–501PubMed
90.
Jacqz-Aigrain E, Bellaich M, Faure C, et al. Pharmacokinetics of intravenous omeprazole in children. Eur J Clin Pharmacol 1994; 47(2): 181–5PubMedCrossRef
91.
Jacqz-Aigrain E, Wood C, Robieux I. Pharmacokinetics of mid-azolam in critically ill neonates. Eur J Clin Pharmacol 1990; 39(2): 191–2PubMedCrossRef
92.
Rey E, Delaunay L, Pons G, et al. Pharmacokinetics of mid-azolam in children: comparative study of intranasal and intravenous administration. Eur J Clin Pharmacol 1991; 41(4): 355–7PubMedCrossRef
93.
Tolia V, Brennan S, Aravind MK, et al. Pharmacokinetic and pharmacodynamic study of midazolam in children during es-ophagogastroduodenoscopy. J Pediatr 1991; 119(3): 467–71PubMedCrossRef
94.
McDermott CA, Kowalczyk AL, Schnitzler ER, et al. Pharmacokinetics of lorazepam in critically ill neonates with seizures. J Pediatr 1992; 120(3): 479–83PubMedCrossRef
95.
Crom WR, Relling MV, Christensen ML, et al. Age-related differences in hepatic drug clearance in children: studies with lorazepam and antipyrine. Clin Pharmacol Ther 1991; 50(2): 132–40PubMedCrossRef
96.
McRorie TI, Lynn AM, Nespeca MK, et al. The maturation of morphine clearance and metabolism [published erratum appears in AmJDis Child 1992 Nov; 146 (11): 1305]. AmJDis Child 1992; 146(8): 972–6
97.
Osborne R, Joel S, Trew D, et al. Morphine and metabolite behavior after different routes of morphine administration: demonstration of the importance of the active metabolite mor-phine-6-glucuronide. Clin Pharmacol Ther 1990; 47(1): 12–9PubMedCrossRef
98.
Lynn AM, Slattery JT. Morphine pharmacokinetics in early infancy. Anesthesiology 1987; 66(2): 136–9PubMedCrossRef
99.
Boucher FD, Modlin JF, Weller S, et al. Phase I evaluation of zidovudine administered to infants exposed at birth to the human immunodeficiency virus. J Pediatr 1993; 122(1): 137–44PubMedCrossRef
100.
Klecker RW Jr, Collins JM, Yarchoan R, et al. Plasma and cerebrospinal fluid pharmacokinetics of 3′-azido-3′-deoxythymidine: a novel pyrimidine analog with potential application for the treatment of patients with AIDS and related diseases. Clin Pharmacol Ther 1987; 41(4): 407–12PubMedCrossRef
101.
Mirochnick M, Capparelli E, Dankner W, et al. Zidovudine pharmacokinetics in premature infants exposed to human immunodeficiency virus. Antimicrob Agents Chemother 1998; 42(4): 808–12PubMed
102.
Pariente-Khayat A, Pons G, Rey E, et al. Caffeine acetylator phenotyping during maturation in infants. Pediatr Res 1991; 29(5): 492–5PubMedCrossRef
103.
Nelson DR, Koymans L, Kamataki T, et al. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics 1996; 6(1): 1–42PubMedCrossRef
104.
Guengerich FP. Catalytic selectivity of human cytochrome P450 enzymes: relevance to drug metabolism and toxicity. Toxicol Lett 1994; 70(2): 133–8PubMedCrossRef
105.
Rane A. Phenotyping of drug metabolism in infants and children: potentials and problems. Pediatrics 1999; 104(3 Pt 2): 640–3PubMed
106.
Tanaka E. Update: genetic polymorphism of drug metabolizing enzymes in humans. J Clin Pharm Ther 1999; 24(5): 323–9PubMedCrossRef
107.
Cresteil T. Onset of xenobiotic metabolism in children: toxico-logical implications. Food Addit Contam 1998; 15: 45–51PubMedCrossRef
108.
Zamboni L. Electron microscopic studies of blood embryogene-sis in humans: I. The ultrastructure of the fetal liver. J Ultra-structRes 1965; 12(5): 509–24CrossRef
109.
110.
Cresteil T, Beaune P, Kremers P, et al. Immunoquantification of epoxide hydrolase and cytochrome P-450 isozymes in fetal and adult human liver microsomes. Eur JBiochem 1985; 151(2): 345–50CrossRef
111.
Nebert DW. Proposed role of drug-metabolizing enzymes: regulation of steady state levels of the ligands that effect growth, homeostasis, differentiation, and neuroendocrine functions. Mol Endocrinol 1991; 5(9): 1203–14PubMedCrossRef
112.
Sonnier M, Cresteil T. Delayed ontogenesis of CYP1A2 in the human liver. Eur J Biochem 1998; 251(3): 893–8PubMedCrossRef
113.
Kearns GL, Reed MD. Clinical pharmacokinetics in infants and children: a reappraisal. Clin Pharmacokinet 1989; 17 Suppl. 1: 29–67PubMedCrossRef
114.
Gilman JT. Therapeutic drug monitoring in the neonate and paediatric age group: problems and clinical pharmacokinetic implications. Clin Pharmacokinet 1990; 19(1): 1–10PubMedCrossRef
115.
116.
Renwick AG. Toxicokinetics in infants and children in relation to the ADI and TDI. Food Addit Contam 1998; 15: 17–35PubMedCrossRef
117.
Gonzalez FJ, Lee YH. Constitutive expression of hepatic cytochrome P450 genes. FASEB J 1996; 10(10): 1112–7PubMed
118.
Gow PJ, Ghabrial H, Smallwood RA, et al. Neonatal hepatic drug elimination. Pharmacol Toxicol 2001; 88(1): 3–15PubMedCrossRef
119.
McCarver DG, Hines RN. The ontogeny of human drug-metabolizing enzymes: phase I oxidative enzymes. J Pharmacol Exp Ther 2002; 300(2): 355–60PubMedCrossRef
120.
McCarver DG, Hines RN. The ontogeny of human drug-metabolizing enzymes: phase II conjugation enzymes and regulatory mechanisms. J Pharmacol Exp Ther 2002; 300(2): 361–6PubMedCrossRef
121.
de Wildt SN, Kearns GL, Leeder JS, et al. Cytochrome P450 3A: ontogeny and drug disposition. Clin Pharmacokinet 1999; 37(6): 485–505PubMedCrossRef
122.
Sesardic D, Pasanen M, Pelkonen O, et al. Differential expression and regulation of members of the cytochrome P450IA gene subfamily in human tissues. Carcinogenesis 1990; 11(7): 1183–8PubMedCrossRef
123.
Ioannides C, Parke DV. Induction of cytochrome P4501 as an indicator of potential chemical carcinogenesis [published erratum appears in Drug Metab Rev 1994; 26 (1–2): 483]. Drug MetabRev 1993; 25(4): 485–501CrossRef
124.
Lee QH, Fantel AG, Juchau MR. Human embryonic cytochrome P450S: phenoxazone ethers as probes for expression of functional isoforms during organogenesis. Biochem Pharmacol 1991; 42(12): 2377–85PubMedCrossRef
125.
Maenpaa J, Pelkonen O, Cresteil T, et al. The role of cytochrome P450 3A (CYP3A) isoform (s) in oxidative metabolism of testosterone and benzphetamine in human adult and fetal liver. J Steroid Biochem Mol Biol 1993; 44(1): 61–7PubMedCrossRef
126.
Hakkola J, Pasanen M, Purkunen R, et al. Expression of xenobiotic-metabolizing cytochrome P450 forms in human adult and fetal liver. Biochem Pharmacol 1994; 48(1): 59–64PubMedCrossRef
127.
Butler MA, Iwasaki M, Guengerich FP, et al. Human cytochrome P-450PA (P-450IA2), the phenacetin O-deethylase, is primarily responsible for the hepatic 3-demethylation of caffeine and N-oxidation of carcinogenic arylamines. Proc Natl Acad Sci U S A 1989; 86(20): 7696–700PubMedCrossRef
128.
Ratanasavanh D, Beaune P, Morel F, et al. Intralobular distribution and quantitation of cytochrome P-450 enzymes in human liver as a function of age. Hepatology 1991; 13(6): 1142–51PubMedCrossRef
129.
Tateishi T, Nakura H, Asoh M, et al. A comparison of hepatic cytochrome P450 protein expression between infancy and postinfancy. Life Sci 1997; 61(26): 2567–74PubMedCrossRef
130.
Goldstein JA, de Morais SM. Biochemistry and molecular biology of the human CYP2C subfamily. Pharmacogenetics 1994; 4(6): 285–99PubMedCrossRef
131.
Pasanen M, Pelkonen O, Kauppila A, et al. Characterization of human fetal hepatic cytochrome P-450-associated 7-ethoxyresorufin O-deethylase and aryl hydrocarbon hy-droxylase activities by monoclonal antibodies. Dev Pharmacol Ther 1987; 10(2): 125–32PubMed
132.
Daly AK, Brockmoller J, Broly F, et al. Nomenclature for human CYP2D6alleles. Pharmacogenetics 1996; 6(3): 193–201PubMedCrossRef
133.
Ladona MG, Lindstrom B, Thyr C, et al. Differential foetal development of the O- and N-demethylation of codeine and dextromethorphan in man. Br J Clin Pharmacol 1991; 32(3): 295–302PubMedCrossRef
134.
Koop DR. Oxidative and reductive metabolism by cytochrome P450 2E1. FASEB J 1992; 6(2): 724–30PubMed
135.
Komori M, Nishio K, Fujitani T, et al. Isolation of anew human fetal liver cytochrome P450 cDNA clone: evidence for expression of a limited number of forms of cytochrome P450 in human fetal livers. Arch Biochem Biophys 1989; 272(1): 219–25PubMedCrossRef
136.
Jones SM, Boobis AR, Moore GE, et al. Expression of CYP2E1 during human fetal development: methylation of the CYP2E1 gene in human fetal and adult liver samples. Biochem Pharmacol 1992; 43(8): 1876–9PubMedCrossRef
137.
Carpenter SP, Lasker JM, Raucy JL. Expression, induction, and catalytic activity of the ethanol-inducible cytochrome P450 (CYP2E1) in human fetal liver and hepatocytes. Mol Pharmacol 1996; 49(2): 260–8PubMed
138.
Nelson DR, Koymans L, Kamataki T, et al. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics 1996; 6(1): 1–42PubMedCrossRef
139.
Jounaidi Y, Hyrailles V, Gervot L, et al. Detection of CYP3A5 allelic variant: a candidate for the polymorphic expression of the protein?. Biochem Biophys Res Commun 1996; 221(2): 466–70PubMedCrossRef
140.
Wrighton SA, Brian WR, Sari MA, et al. Studies on the expression and metabolic capabilities of human liver cytochrome P450IIIA5 (HLp3). Mol Pharmacol 1990; 38(2): 207–13PubMed
141.
Schuetz JD, Beach DL, Guzelian PS. Selective expression of cytochrome P450 CYP3A mRNAs in embryonic and adult human liver. Pharmacogenetics 1994; 4(1): 11–20PubMedCrossRef
142.
Wrighton SA, Ring BJ, Watkins PB, et al. Identification of a polymorphically expressed member of the human cytochrome P-450III family. Mol Pharmacol 1989; 36(1): 97–105PubMed
143.
Kuehl P, Zhang J, Lin Y, et al. Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression. Nat Genet 2001; 27(4): 383–91PubMedCrossRef
144.
Aoyama T, Yamano S, Waxman DJ, et al. Cytochrome P-450 hPCN3, a novel cytochrome P-450 IIIA gene product that is differentially expressed in adult human liver. cDNA and deduced amino acid sequence and distinct specificities of cDNA-expressed hPCNl and hPCN3 for the metabolism of steroid hormones and cyclosporine. J Biol Chem 1989; 264(18): 10388–95PubMed
145.
Gillam EM, Guo Z, Ueng YF, et al. Expression of cytochrome P450 3A5 in Escherichia coli: effects of 5′modification, purification, spectral characterization, reconstitution conditions, and catalytic activities. Arch Biochem Biophys 1995; 317(2): 374–84PubMedCrossRef
146.
Raucy JL, Carpenter SJ. The expression of xenobiotic-metabo-lizing cytochromes P450 in fetal tissues. J Pharmacol Toxicol Methods 1993; 29(3): 121–8PubMedCrossRef
147.
Kitada M, Kamataki T. Cytochrome P450 in human fetal liver: significance and fetal-specific expression. Drug Metab Rev 1994; 26(1–2): 305–23PubMedCrossRef
148.
Kitada M, Kamataki T, Itahashi K, et al. Significance of cytochrome P-450 (P-450 HFLa) of human fetal livers in the ste-roid and drug oxidations. Biochem Pharmacol 1987; 36(4): 453–6PubMedCrossRef
149.
Kitada M, Kamataki T, Itahashi K, et al. P-450 HFLa, a form of cytochrome P-450 purified from human fetal livers, is the 16 alpha-hydroxylase of dehydroepiandrosterone 3-sulfate. J Biol Chem 1987; 262(28): 13534–7PubMed
150.
Komori M, Nishio K, Kitada M, et al. Fetus-specific expression of a form of cytochrome P-450 in human livers. Biochemistry 1990; 29(18): 4430–3PubMedCrossRef
151.
Hashimoto H, Toide K, Kitamura R, et al. Gene structure of CYP3A4, an adult-specific form of cytochrome P450 in human livers, and its transcriptional control. Eur J Biochem 1993; 218(2): 585–95PubMedCrossRef
152.
Ohmori S, Fujiki N, Nakasa H, et al. Steroid hydroxylation by human fetal CYP3A7 and human NADPH-cytochrome P450 reductase coexpressed in insect cells using baculovirus. Res Commun Mol Pathol Pharmacol 1998; 100(1): 15–28PubMed
153.
Burtin P, Jacqz-Aigrain E, Girard P, et al. Population pharma-cokinetics of midazolam in neonates. Clin Pharmacol Ther 1994; 56(6 Pt 1): 615–25PubMedCrossRef
154.
Payne K, Mattheyse FJ, Liebenberg D, et al. The pharmacoki-netics of midazolam in paediatric patients. Eur J Clin Pharmacol 1989; 37(3): 267–72PubMedCrossRef
155.
156.
Rappaport AM. Physioanatomic consideration. In: Schiff ER, editor. Disease of the Liver. Philadelphia (PA): JB Lippincott, 1987: 1–46
157.
Fukuda T. Fetal hemopoiesis. II. Electron microscopic studies on human hepatic hemopoiesis. Virchows Arch B Cell Pathol 1974; 16(3): 249–70PubMedCrossRef
158.
Feracci H, Connolly TP, Margolis RN, et al. The establishment of hepatocyte cell surface polarity during fetal liver development. Dev Biol 1987; 123(1): 73–84PubMedCrossRef
159.
Jones CT, Rolph TP. Metabolism during fetal life: a functional assessment of metabolic development. Physiol Rev 1985; 65(2): 357–430PubMed
160.
Murao F, Takamori H, Aoki S, et al. Ultrasonographic measurement of the human fetal liver in utero. Gynecol Obstet Invest 1987; 24(3): 145–50PubMedCrossRef
161.
Widdowson EM, Crabb DE, Milner RD. Cellular development of some human organs before birth. Arch Dis Child 1972; 47(254): 652–5PubMedCrossRef
162.
Greengard O, Federman M, Knox WE. Cytomorphometry of developing rat liver and its application to enzymic differentiation. J Cell Biol 1972; 52(2): 261–72PubMedCrossRef
163.
Stave U. Liver enzymes. In: Stave U, editor. Perinatal physiology. New York: Plenum Medical Book Company, 1978: 499–521CrossRef
164.
Swartz FJ. The development in the human liver of multiple deoxyribose nucleic acid (DNA) classes and their relationship to the age of the individual. Chromosoma 1956; 8: 53PubMedCrossRef
165.
Groothuis GM, Meijer DK. Hepatocyte heterogeneity in bile formation and hepatobiliary transport of drugs. Enzyme 1992; 46(1–3): 94–128PubMed
166.
Lamers WH, Gaasbeek Janzen JW, Kortschot AT, et al. Development of enzymic zonation in liver parenchyma is related to development of acinar architecture. Differentiation 1987; 35(3): 228–35PubMedCrossRef
167.
Wagenaar GT, Chamuleau RA, de Haan JG, et al. Experimental evidence that the physiological position of the liver within the circulation is not a major determinant of zonation of gene expression. Hepatology 1993; 18(5): 1144–53PubMedCrossRef
168.
Montagnani CA. Intrahepatic vascular pattern in the newborn infant. Ann N Y Acad Sci 1963; 111: 121–35PubMedCrossRef
169.
Watkins JB, Ingall D, Szczepanik P, et al. Bile-salt metabolism in the newborn: measurement of pool size and synthesis by stable isotope technique. N Engl J Med 1973; 288(9): 431–4PubMedCrossRef
170.
Tavoloni N. Bile secretion and its control in the newborn puppy. PediatrRes 1986; 20(3): 203–8
171.
Tavoloni N, Jones MJ, Berk PD. Postnatal development of bile secretory physiology in the dog. J Pediatr Gastroenterol Nutr 1985; 4(2): 256–67PubMedCrossRef
172.
Krauer B, Dayer P. Fetal drug metabolism and its possible clinical implications. Clin Pharmacokinet 1991; 21(1): 70–80PubMedCrossRef
173.
Coughtrie MW, Bamforth KJ, Sharp S, et al. Sulfation of endogenous compounds and xenobiotics: interactions and function in health and disease. Chem Biol Interact 1994; 92(1–3): 247–56PubMedCrossRef
174.
Coughtrie MW, Burchell B, Leakey JE, et al. The inadequacy of perinatal glucuronidation: immunoblot analysis of the developmental expression of individual UDP-glucuronosyl-transferase isoenzymes in rat and human liver microsomes. Mol Pharmacol 1988; 34(6): 729–35PubMed
175.
Leakey JE, Hume R, Burchell B. Development of multiple activities of UDP-glucuronyltransferase in human liver. Biochem J 1987; 243(3): 859–61PubMed
176.
Pacifici GM, Franchi M, Colizzi C, et al. Sulfotransferase in humans: development and tissue distribution. Pharmacology 1988; 36(6): 411–9PubMedCrossRef
177.
Cappiello M, Giuliani L, Rane A, et al. Dopamine sulpho-transferase is better developed than p-nitrophenol sul-photransferase in the human fetus. Dev Pharmacol Ther 1991; 16(2): 83–8PubMed
178.
Strange RC, Howie AF, Hume R, et al. The development expression of alpha-, mu- and pi-class glutathione S-transfer-ases in human liver. Biochim Biophys Acta 1989; 993(2–3): 186–90PubMedCrossRef
179.
Pacifici GM, Franchi M, Colizzi C, et al. Glutathione S-trans-ferase in humans: development and tissue distribution. Arch Toxicol 1988; 61(4): 265–9PubMedCrossRef
180.
Cappiello M, Giuliani L, Pacifici GM. Differential distribution of phenol and catechol sulphotransferases in human liver and intestinal mucosa. Pharmacology 1990; 40(2): 69–76PubMedCrossRef
181.
Meisel M, Schneider T, Siegmund W, et al. Development of human polymorphic N-acetyltransferase. Biol Res Pregnancy Perinatol 1986; 7(2): 74–6PubMed
182.
Mackenzie PI, Owens IS, Burchell B, et al. The UDP glyco-syltransferase gene superfamily: recommended nomenclature update based on evolutionary divergence. Pharmacogenetics 1997; 7(4): 255–69PubMedCrossRef
183.
de Wildt SN, Kearns GL, Leeder JS, et al. Glucuronidation in humans. Pharmacogenetic and developmental aspects. Clin Pharmacokinet 1999; 36(6): 439–52PubMedCrossRef
184.
Ritter JK, Chen F, Sheen YY, et al. A novel complex locus UGT1 encodes human bilirubin, phenol, and other UDP-glucuronosyltransferase isozymes with identical carboxyl termini. J Biol Chem 1992; 267(5): 3257–61PubMed
185.
Clarke DJ, Moghrabi N, Monaghan G, et al. Genetic defects of the UDP-glucuronosyltransferase-1 (UGT1) gene that cause familial non-haemolytic unconjugated hyperbilirubinaemias. Clin Chim Acta 1997; 266(1): 63–74PubMedCrossRef
186.
Monaghan G, Clarke DJ, Povey S, et al. Isolation of a human YAC contig encompassing a cluster of UGT2 genes and its regional localization to chromosome 4ql3. Genomics 1994; 23(2): 496–9PubMedCrossRef
187.
King CD, Rios GR, Assouline JA, et al. Expression of UDP-glucuronosyltransferases (UGTs) 2B7 and 1A6 in the human brain and identification of 5-hydroxytryptamine as a substrate. Arch Biochem Biophys 1999; 365(1): 156–62PubMedCrossRef
188.
Burchell B, Coughtrie MW. Genetic and environmental factors associated with variation of human xenobiotic glucuronidation and sulfation. Environ Health Perspect 1997; 105 Suppl. 4: 739–47PubMed
189.
Strassburg CP, Nguyen N, Manns MP, et al. UDP-glucuronosyltransferase activity in human liver and colon. Gastroen-terology 1999; 116(1): 149–60CrossRef
190.
Ebner T, Burchell B. Substrate specificities of two stably expressed human liver UDP-glucuronosyltransferases of the UGT1 gene family. Drug Metab Dispos 1993; 21(1): 50–5PubMed
191.
Dutton GJ. Developmental aspects of drug conjugation, with special reference to glucuronidation. Annu Rev Pharmacol Toxicol 1978; 18: 17–35PubMedCrossRef
192.
Rane A, Tomson G. Prenatal and neonatal drug metabolism in man. Eur J Clin Pharmacol 1980; 18(1): 9–15PubMedCrossRef
193.
Rollins DE, von Bahr C, Glaumann H, et al. Acetaminophen: potentially toxic metabolite formed by human fetal and adult liver microsomes and isolated fetal liver cells. Science 1979; 205(4413): 1414–6PubMedCrossRef
194.
Burchell B, Coughtrie M, Jackson M, et al. Development of human liver UDP-glucuronosyltransferases. Dev Pharmacol Ther 1989; 13(2–4): 70–7PubMed
195.
Hume R, Coughtrie MW, Burchell B. Differential localisation of UDP-glucuronosyltransferase in kidney during human embryonic and fetal development. Arch Toxicol 1995; 69(4): 242–7PubMedCrossRef
196.
Hume R, Burchell A, Allan BB, et al. The ontogeny of key endoplasmic reticulum proteins in human embryonic and fetal red blood cells. Blood 1996; 87(2): 762–70PubMed
197.
Mikkelsen S, Feilberg VL, Christensen CB, et al. Morphine pharmacokinetics in premature and mature newborn infants. Acta Paediatr 1994; 83(10): 1025–8PubMedCrossRef
198.
Onishi S, Kawade N, Itoh S, et al. Postnatal development of uridine diphosphate glucuronyltransferase activity towards bilirubin and 2-aminophenol in human liver. Biochem J 1979; 184(3): 705–7PubMed
199.
Pacifici GM, Franchi M, Giuliani L, et al. Development of the glucuronyltransferase and sulphotransferase towards 2-naph-thol in human fetus. Dev PharmacolTher 1989; 14(2): 108–14
200.
Pacifici GM, Sawe J, Kager L, et al. Morphine glucuronidation in human fetal and adult liver. Eur J Clin Pharmacol 1982; 22(6): 553–8PubMedCrossRef
201.
Anderson BJ, McKee AD, Holford NH. Size, myths and the clinical pharmacokinetics of analgesia in paediatric patients. Clin Pharmacokinet 1997; 33(5): 313–27PubMedCrossRef
202.
Choonara IA, McKay P, Hain R, et al. Morphine metabolism in children. Br J Clin Pharmacol 1989; 28(5): 599–604PubMedCrossRef
203.
Barker EV, Hume R, Hallas A, et al. Dehydroepiandrosterone sulfotransferase in the developing human fetus: quantitative biochemical and immunological characterization of the hepatic, renal, and adrenal enzymes. Endocrinology 1994; 134(2): 982–9PubMedCrossRef
204.
Falany CN. Molecular enzymology of human liver cytosolic sulfotransferases. Trends Pharmacol Sci 1991; 12(7): 255–9PubMedCrossRef
205.
Campbell NR, Van Loon JA, Weinshilboum RM. Human liver phenol sulfotransferase: assay conditions, biochemical properties and partial purification of isozymes of the thermostable form. Biochem Pharmacol 1987; 36(9): 1435–46PubMedCrossRef
206.
Richard K, Hume R, Kaptein E, et al. Sulfation of thyroid hormone and dopamine during human development: ontogeny of phenol sulfotransferases and arylsulfatase in liver, lung, and brain. J Clin Endocrinol Metab 2001; 86(6): 2734–42PubMedCrossRef
207.
Pacifici GM, Kubrich M, Giuliani L, et al. Sulphation and glucuronidation of ritodrine in human foetal and adult tissues. Eur J Clin Pharmacol 1993; 44(3): 259–64PubMedCrossRef
208.
Gilissen RA, Hume R, Meerman JH, et al. Sulphation of N-hydroxy-4-aminobiphenyl and N-hydroxy-4-acetylamino-biphenyl by human foetal and neonatal sulphotransferase. Biochem Pharmacol 1994; 48(4): 837–40PubMedCrossRef
209.
Mannervik B, Danielson UH. Glutathione transferases: structure and catalytic activity. CRC Crit Rev Biochem 1988; 23(3): 283–337PubMedCrossRef
210.
Soma Y, Satoh K, Sato K. Purification and subunit-structural and immunological characterization of five glutathione S-transferases in human liver, and the acidic form as a hepatic tumor marker. Biochim Biophys Acta 1986; 869(3): 247–58PubMedCrossRef
211.
Mannervik B, Awasthi YC, Board PG, et al. Nomenclature for human glutathione transferases [letter]. Biochem J 1992; 282(Pt 1): 305–6PubMed
212.
Mitra A, Govindwar S, Joseph P, et al. Inhibition of human term placental and fetal liver glutathione-S-transferases by fatty acids and fatty acid esters. Toxicol Lett 1992; 60(3): 281–8PubMedCrossRef
213.
Mera N, Ohmori S, Itahashi K, et al. Immunochemical evidence for the occurrence of Mu class glutathione S-transferase in human fetal livers. J Biochem (Tokyo) 1994; 116(2): 315–20
214.
Strange RC, Davis BA, Faulder CG, et al. The human glutathione S-transferases: developmental aspects of the GST1, GST2, and GST3 loci. Biochem Genet 1985; 23(11–12): 1011–28PubMedCrossRef
215.
Vos RM, Van Bladeren PJ. Glutathione S-transferases in relation to their role in the biotransformation of xenobiotics. Chem Biol Interact 1990; 75(3): 241–65PubMedCrossRef
216.
Pacifici GM, Warholm M, Guthenberg C, et al. Organ distribution of glutathione transferase isoenzymes in the human fetus: differences between liver and extrahepatic tissues. Biochem Pharmacol 1986; 35(9): 1616–9PubMedCrossRef
217.
Guthenberg C, Warholm M, Rane A, et al. Two distinct forms of glutathione transferase from human foetal liver: purification and comparison with isoenzymes isolated from adult liver and placenta. Biochem J 1986; 235(3): 741–5PubMed
218.
Mathew J, Cattan AR, Hall AG, et al. Glutathione S-transferases in neonatal liver disease. J Clin Pathol 1992; 45(8): 679–83PubMedCrossRef
219.
Kashiwada M, Kitada M, Shimada T, et al. Purification and characterization of acidic form of glutathione S-transferase in human fetal livers: high similarity to placental form. J Biochem (Tokyo) 1991; 110(5): 743–7
220.
Warholm M, Guthenberg C, Mannervik B, et al. Purification of a new glutathione S-transferase (transferase mu) from human liver having high activity with benzo (alpha)pyrene-4,5-ox-ide. Biochem Biophys Res Commun 1981; 98(2): 512–9PubMedCrossRef
221.
Holt DE, Hurley R, Harvey D. Metabolism of chloramphenicol by glutathione S-transferase in human fetal and neonatal liver. Biol Neonate 1995; 67(4): 230–9PubMedCrossRef
222.
Pacifici GM, Boobis AR, Brodie MJ, et al. Tissue and species differences in enzymes of epoxide metabolism. Xenobiotica 1981; 11(2): 73–9PubMedCrossRef
223.
Pacifici GM, Norlin A, Rane A. Glutathione-S-transferase in human fetal liver. Biochem Pharmacol 1981; 30(24): 3367–71PubMedCrossRef
224.
Baars AJ, Mukhtar H, Zoetemelk CE, et al. Glutathione S-transferase activity in rat and human tissues and organs. Comp Biochem Physiol C 1981; 70(2): 285–8PubMedCrossRef
225.
Mukhtar H, Zoetemelk CE, Baars AJ, et al. Glutathione S-transferase activity in human fetal and adult tissues. Pharmacology 1981; 22(5): 322–9PubMedCrossRef
226.
Faulder CG, Hirrell PA, Hume R, et al. Studies of the development of basic, neutral and acidic isoenzymes of glutathione S-transferase in human liver, adrenal, kidney and spleen. Biochem J 1987; 241(1): 221–8PubMed
227.
Pacifici GM, Bencini C, Rane A. Acetyltransferase in humans: development and tissue distribution. Pharmacology 1986; 32(5): 283–91PubMedCrossRef
228.
Ohsako S, Deguchi T. Cloning and expression of cDNAs for polymorphic and monomorphic arylamine N-acetyltrans-ferases from human liver. J Biol Chem 1990; 265(8): 4630–4PubMed
229.
Grant DM, Blum M, Beer M, et al. Monomorphic and polymorphic human arylamine N-acetyltransferases: a comparison of liver isozymes and expressed products of two cloned genes. Mol Pharmacol 1991; 39(2): 184–91PubMed
230.
Ilett KF, Kadlubar FF, Minchin RF. 1998 International meeting on the arylamine N-acetyltransferases: synopsis of the workshop on nomenclature, biochemistry, molecular biology, in-terspecies comparisons, and role in human disease risk. Drug Metab Dispos 1999; 27(9): 957–9PubMed
231.
Peng DR, Birgersson C, von Bahr C, et al. Polymorphic acety-lation of 7-amino-clonazepam in human liver cytosol. Pediatr Pharmacol 1984; 4(3): 155–9
232.
Fichter EG, Curtis JA. Sulfonamide administration in newborn and premature infants. Am J Dis Child 1955; 90: 596–7
233.
Szorady I, Santa A, Veress I. Drug acetylator phenotypes in newborn infants. Biol Res Pregnancy Perinatol 1987; 8(1): 23–5PubMed
234.
Pariente-Khayat A, Rey E, Gendrel D, et al. Isoniazid acetylation metabolic ratio during maturation in children. Clin Pharmacol Ther 1997; 62(4): 377–83PubMedCrossRef
235.
Brazier JL, Salle B, Ribon B, et al. In vivo N7 methylation of theophylline to caffeine in premature infants: studies with use of stable isotopes. Dev Pharmacol Ther 1981; 2(3): 137–44PubMed
236.
Haley TJ. Metabolism and pharmacokinetics of theophylline in human neonates, children, and adults. Drug Metab Rev 1983; 14(2): 295–335PubMedCrossRef
237.
Rosen T, Schimmel MS. A short review of perinatal pharmacology. Bull N Y Acad Med 1983; 59(7): 669–77PubMed
238.
O’Donnell J. Theophylline misadventures: part I. Neonatal Netw 1994; 13(2): 35–43PubMed
239.
O’Donnell J. Theophylline misadventures: part II. Neonatal Netw 1994; 13(3): 19–28PubMed
240.
Anderson BJ, Gunn TR, Holford NH, et al. Caffeine overdose in a premature infant: clinical course and pharmacokinetics. Anaesth Intensive Care 1999; 27(3): 307–11PubMed
241.
Kraus DM, Fischer JH, Reitz SJ, et al. Alterations in theophylline metabolism during the first year of life. Clin Pharmacol Ther 1993; 54(4): 351–9PubMedCrossRef
242.
Levy G, Khanna NN, Soda DM, et al. Pharmacokinetics of acetaminophen in the human neonate: formation of acetaminophen glucuronide and sulfate in relation to plasma bilirubin concentration and D-glucaric acid excretion. Pediatrics 1975; 55(6): 818–25PubMed
243.
Alam SN, Roberts RJ, Fischer LJ. Age-related differences in salicylamide and acetaminophen conjugation in man. J Pediatr 1977; 90(1): 130–5PubMedCrossRef
244.
Done AK, Cohen SN, Strebel L. Pediatric clinical pharmacology and the therapeutic orphan. Annu Rev Pharmacol Toxicol 1977; 17: 561–73PubMedCrossRef
245.
Miller RP, Roberts RJ, Fischer LJ. Acetaminophen elimination kinetics in neonates, children, and adults. Clin Pharmacol Ther 1976; 19(3): 284–94PubMed
246.
Brashear WT, Kuhnert BR, Wei R. Maternal and neonatal urinary excretion of sulfate and glucuronide ritodrine conjugates. Clin Pharmacol Ther 1988; 44(6): 634–41PubMedCrossRef
247.
Neims AH, Warner M, Loughnan PM, et al. Developmental aspects of the hepatic cytochrome P450 monooxygenase system. Annu Rev Pharmacol Toxicol 1976; 16: 427–45PubMedCrossRef
248.
Loughnan PM, Greenwald A, Purton WW, et al. Pharmacoki-netic observations of phenytoin disposition in the newborn and young infant. Arch Dis Child 1977; 52(4): 302–9PubMedCrossRef
249.
Sereni F, Mandelli M, Principi N, et al. Induction of drug metabolizing enzyme activities in the human fetus and in the newborn infant. Enzyme 1973; 15(1): 318–29PubMed
250.
251.
Rating D, Jager-Roman E, Nau H, et al. Enzyme induction in neonates after fetal exposure to antiepileptic drugs. Pediatr Pharmacol 1983; 3(3–4): 209–18
252.
Boreus LO. The role of therapeutic drug monitoring in children. Clin Pharmacokinet 1989; 17 Suppl. 1: 4–12PubMedCrossRef
253.
Perrot N, Nalpas B, Yang CS, et al. Modulation of cytochrome P450 isozymes in human liver, by ethanol and drug intake. Eur J Clin Invest 1989; 19(6): 549–55PubMedCrossRef
254.
Furuya H, Meyer UA, Gelboin HV, et al. Polymerase chain reaction-directed identification, cloning, and quantification of human CYP2C18 mRNA. Mol Pharmacol 1991; 40(3): 375–82PubMed
255.
Lin JH, Lu AY. Inhibition and induction of cytochrome P450 and the clinical implications. Clin Pharmacokinet 1998; 35(5): 361–90PubMedCrossRef
256.
Nemeth AM. The regulation of liver development by birth. Enzyme 1973; 15(1): 286–95PubMed
257.
Mannering GJ. Drug metabolism in the newborn. Fed Proc 1985; 44(7): 2302–8PubMed
258.
de Morais SM, Schweikl H, Blaisdell J, et al. Gene structure and upstream regulatory regions of human CYP2C9 and CYP2C18. Biochem Biophys Res Commun 1993; 194(1): 194–201PubMedCrossRef
259.
Jounaidi Y, Guzelian PS, Maurel P, et al. Sequence of the 5′-flanking region of CYP3A5: comparative analysis with CYP3A4 and CYP3A7. Biochem Biophys Res Commun 1994; 205(3): 1741–7PubMedCrossRef
260.
Ibeanu GC, Goldstein JA. Transcriptional regulation of human CYP2C genes: functional comparison of CYP2C9 and CYP2C18 promoter regions. Biochemistry 1995; 34(25): 8028–36PubMedCrossRef
261.
Ueno T, Gonzalez FJ. Transcriptional control of the rat hepatic CYP2E1 gene. Mol Cell Biol 1990; 10(9): 4495–505PubMed
262.
Liu SY, Gonzalez FJ. Role of the liver-enriched transcription factor HNF-1 alpha in expression of the CYP2E1 gene. DNA Cell Biol 1995; 14(4): 285–93PubMedCrossRef
263.
Song BJ, Gelboin HV, Park SS, et al. Complementary DNA and protein sequences of ethanol-inducible rat and human cytochrome P-450s. Transcriptional and post-transcriptional regulation of the rat enzyme [published erratum appears in J Biol Chem 1987; 262 (18): 8940]. J Biol Chem 1986; 261(35): 16689–97PubMed
264.
Guignard JP, Torrado A, Da Cunha O, et al. Glomerular filtration rate in the first three weeks of life. J Pediatr 1975; 87(2): 268–72PubMedCrossRef
265.
Leake RD, Trygstad CW. Glomerular filtration rate during the period of adaptation to extrauterine life. Pediatr Res 1977; 11(9 Pt 1): 959–62PubMedCrossRef
266.
Arant Jr BS. Developmental patterns of renal functional maturation compared in the human neonate. J Pediatr 1978; 92(5): 705–12PubMedCrossRef
267.
Strauss J, Daniel SS, James LS. Postnatal adjustment in renal function. Pediatrics 1981; 68(6): 802–8PubMed
268.
Halkin H, Radomsky M, Millman P, et al. Steady state serum concentrations and renal clearance of digoxin in neonates, infants and children. Eur J Clin Pharmacol 1978; 13(2): 113–7PubMedCrossRef
269.
Ng PK, Cote J, Schiff D, et al. Renal clearance of digoxin in premature neonates. Res Commun Chem Pathol Pharmacol 1981; 34(2): 207–16PubMed
270.
Haycock GB. Development of glomerular filtration and tubular sodium reabsorption in the human fetus and newborn. Br J Urol 1998; 81 Suppl. 2: 33–8PubMed
271.
Potter EL. Normal and abnormal development of the kidney. Chicago (IL): Year Book Medical Publishers, 1972
272.
duBois AM. The embryonic kidney. In: Muller AF, editor. The Kidney. New York: Academic Press, 1969: 1–59
273.
McCrory WW. Developmental nephrology. Cambridge: Harvard University Press, 1972
274.
MacDonald MS, Emery JL. The late intrauterine and postnatal development of human renal glomeruli. J Anat 1959; 93: 331–41PubMed
275.
Potter EL. Development of the human glomerulus. Arch Pathol 1965; 80: 241PubMed
276.
Robillard JE, Kulvinskas C, Sessions C, et al. Maturational changes in the fetal glomerular filtration rate. Am J Obstet Gynecol 1975; 122(5): 601–6PubMed
277.
Robillard JE, Sessions C, Kennedey RL, et al. Interrelationship between glomerular filtration rate and renal transport of sodium and chloride during fetal life. Am J Obstet Gynecol 1977; 128(7): 727–34PubMed
278.
Lumbers ER, Stevens AD. Factors influencing glomerular filtration rate in the fetal lamb [proceedings]. J Physiol 1980; 298: 28P–9PPubMed
279.
Leake RD, Trygstad CW, Oh W. Inulin clearance in the newborn infant: relationship to gestational and postnatal age. Pediatr Res 1976; 10(8): 759–62PubMed
280.
Fetterman GH, Shyplock NA, Philipp F, et al. The growth and maturation of human glomeruli and proximal convolutions from term to adulthood. Pediatrics 1965; 35: 601–19PubMed
281.
282.
Rane A, Wilson JT. Clinical pharmacokinetics in infants and children. Clin Pharmacokinet 1976; 1(1): 2–24PubMedCrossRef
283.
Hayton WL. Maturation and growth of renal function: dosing renally cleared drugs in children. AAPS PharmSci 2000; 2 (1): article 3
284.
Barnett HL, McNamara H, Schultz S, et al. Renal clearances of penicillin G, procaine penicillin G, and inulin in infants and children. Pediatrics 1949; 3: 418–22PubMed
285.
Barnett HL, Vesterdal J. The physiologic and clinical significance of immaturity of kidney function in young infants. J Pediatr 1953; 42: 99–119CrossRef
286.
Rubin M, Bruck E, Rapoport M. Maturation of renal function in childhood: clearance studies. J Clin Invest 1949; 28: 1144–62CrossRef
287.
Fawer CL, Torrado A, Guignard JP. Maturation of renal function in full-term and premature neonates. Helv Paediatr Acta 1979; 34(1): 11–21PubMed
288.
Heilbron DC, Holliday MA, al-Dahwi A, et al. Expressing glo-merular filtration rate in children. Pediatr Nephrol 1991; 5(1): 5–11PubMedCrossRef
289.
Oh W, Oh MA, Lind J. Renal function and blood volume in newborn infants related to placental transfusion. Acta Paediatr Scand 1966; 55: 197–210CrossRef
290.
Gordjani N, Burghard R, Leititis JU, et al. Serum creatinine and creatinine clearance in healthy neonates and prematures during the first lOdays of life. EurJPediatr 1988; 148(2): 143–5
291.
Aperia A, Broberger O, Elinder G, et al. Postnatal development of renal function in pre-term and full-term infants. Acta Paediatr Scand 1981; 70(2): 183–7PubMedCrossRef
292.
Sonntag J, Prankel B, Waltz S. Serum creatinine concentration, urinary creatinine excretion and creatinine clearance during the first 9 weeks in preterm infants with a birth weight below 1500g. Eur J Pediatr 1996; 155(9): 815–9PubMedCrossRef
293.
Nakae S, Yamada M, Ito T, et al. Gentamicin dosing and phar-macokinetics in low birth weight infants. Tohoku J Exp Med 1988; 155(3): 213–23PubMedCrossRef
294.
Pons G, d’Athis P, Rey E, et al. Gentamicin monitoring in neonates. Ther Drug Monit 1988; 10(4): 421–7PubMedCrossRef
295.
Rodvold KA, Everett JA, Pryka RD, et al. Pharmacokinetics and administration regimens of vancomycin in neonates, infants and children. Clin Pharmacokinet 1997; 33(1): 32–51PubMedCrossRef
296.
Lisby-Sutch SM, Nahata MC. Dosage guidelines for the use of vancomycin based on its pharmacokinetics in infants. Eur J Clin Pharmacol 1988; 35(6): 637–42PubMedCrossRef
297.
Hoie EB, Swigart SA, Leuschen MP, et al. Vancomycin pharmacokinetics in infants undergoing extracorporeal membrane oxygenation. Clin Pharm 1990; 9(9): 711–5PubMed
298.
Buck ML. Vancomycin pharmacokinetics in neonates receiving extracorporeal membrane oxygenation. Pharmacotherapy 1998; 18(5): 1082–6PubMed
299.
Asbury WH, Darsey EH, Rose WB, et al. Vancomycin pharmacokinetics in neonates and infants: a retrospective evaluation. Ann Pharmacother 1993; 27(4): 490–6PubMed
300.
Gous AG, Dance MD, Lipman J, et al. Changes in vancomycin pharmacokinetics in critically ill infants. Anaesth Intensive Care 1995; 23(6): 678–82PubMed
301.
302.
West JR, Smith HW, Chasis H. Glomerular filtration rate, effective renal blood flow, and maximal tubular excretory capacity in infancy. J Pediatr 1948; 32: 10–8PubMedCrossRef
303.
Glickstein JS, Friedman D. Developmental changes in renal blood flow velocity [abstract]. J Pediatr 1997; 130(2): 336PubMed
304.
Cleary GM, Higgins ST, Merton DA, et al. Developmental changes in renal artery blood flow velocity during the first three weeks of life in preterm neonates. J Pediatr 1996; 129(2): 251–7PubMedCrossRef
305.
Aperia A, Broberger O, Herin P, et al. Renal hemodynamics in the perinatal period: a study in lambs. Acta Physiol Scand 1977; 99(3): 261–9PubMedCrossRef
306.
Gruskin AB, Edelmann Jr CM, Yuan S. Maturational changes in renal blood flow in piglets. Pediatr Res 1970; 4(1): 7–13PubMedCrossRef
307.
John E, Goldsmith DI, Spitzer A. Quantitative changes in the canine glomerular vasculature during development: physiologic implications. Kidney Int 1981; 20(2): 223–9PubMedCrossRef
308.
Mihaly GW, Moore RG, Thomas J, et al. The pharmacokinetics and metabolism of the anilide local anaesthetics in neonates. I. Lignocaine. Eur J Clin Pharmacol 1978; 13(2): 143–52PubMedCrossRef
309.
Larsson L, Maunsbach AB. The ultrastructural development of the glomerular filtration barrier in the rat kidney: a morpho-metric analysis. J Ultrastruct Res 1980; 72(3): 392–406PubMedCrossRef
310.
Gladtke E. The rate of development of elimination functions in kidney and liver of young infants. New York: Raven Press, 1975
311.
Blowey DL, Ben-David S, Koren G. Interactions of drugs with the developing kidney. Pediatr Clin North Am 1995; 42(6): 1415–31PubMed
312.
Nakamura KT, Matherne GP, McWeeny OJ, et al. Renal hemodynamics and functional changes during the transition from fetal to newborn life in sheep. Pediatr Res 1987; 21(3): 229–34PubMedCrossRef
313.
Smith FG, Lumbers ER. Comparison of renal function in term fetal sheep and newborn lambs. Biol Neonate 1989; 55(4–5): 309–16PubMed
314.
Besunder JB, Reed MD, Blumer JL. Principles of drug bio-disposition in the neonate: a critical evaluation of the phar-macokinetic-pharmacodynamic interface (Part II). Clin Pharmacokinet 1988; 14(5): 261–86PubMedCrossRef
315.
Besunder JB, Reed MD, Blumer JL. Principles of drug biodisposition in the neonate: a critical evaluation of the phar-macokinetic-pharmacodynamic interface (Part I). Clin Pharmacokinet 1988; 14(4): 189–216PubMedCrossRef
316.
Calcagno P, Rubin M. Renal extraction of paraaminohippurate in infants and children. J Clin Invest 1963; 42: 1632–9PubMedCrossRef
317.
Siegel SR, Oh W. Renal function as a marker of human fetal maturation. Acta Paediatr Scand 1976; 65(4): 481–5PubMedCrossRef
318.
Kasik JW, Jenkins S, Leuschen MP, et al. Postconceptional age and gentamicin elimination half-life. J Pediatr 1985; 106(3): 502–5PubMedCrossRef
319.
van den Anker JN, de Groot R, Broerse HM, et al. Assessment of glomerular filtration rate in preterm infants by serum creatinine: comparison with inulin clearance. Pediatrics 1995; 96(6): 1156–8PubMed
320.
van der Heijden AJ, Grose WF, Ambagtsheer JJ, et al. Glomerular filtration rate in the preterm infant: the relation to gestational and postnatal age. Eur J Pediatr 1988; 148(1): 24–8PubMedCrossRef
321.
Koren G, James A, Perlman M. A simple method for the estimation of glomerular filtration rate by gentamicin pharmacokinetics during routine drug monitoring in the newborn. Clin Pharmacol Ther 1985; 38(6): 680–5PubMedCrossRef
322.
Zarowitz BJ, Robert S, Peterson EL. Prediction of glomerular filtration rate using aminoglycoside clearance in critically ill medical patients. Ann Pharmacother 1992; 26(10): 1205–10PubMed
323.
Manzke H, Spreter von Kreudenstein P, Dorner K, et al. Quantitative measurements of the urinary excretion of creatinine, uric acid, hypoxanthine and xanthine, uracil, cyclic AMP, and cyclic GMP in healthy newborn infants. Eur J Pediatr 1980; 133(2): 157–61PubMedCrossRef
324.
Fattinger K, Vozeh S, Olafsson A, et al. Netilmicin in the neonate: population pharmacokinetic analysis and dosing recommendations. Clin Pharmacol Ther 1991; 50(1): 55–65PubMedCrossRef
325.
Carrie BJ, Golbetz HV, Michaels AS, et al. Creatinine: an inadequate filtration marker in glomerular diseases. Am J Med 1980; 69(2): 177–82PubMedCrossRef
326.
Bauer JH, Brooks CS, Burch RN. Clinical appraisal of creatinine clearance as a measurement of glomerular filtration rate. Am J Kidney Dis 1982; 2(3): 337–46PubMed
327.
328.
Coulthard MG. Comparison of methods of measuring renal function in preterm babies using inulin. J Pediatr 1983; 102(6): 923–30PubMedCrossRef
329.
Aperia A, Larsson L. Correlation between fluid reabsorption and proximal tubule ultrastructure during development of the rat kidney. Acta Physiol Scand 1979; 105(1): 11–22PubMedCrossRef
330.
Yaffe SJ. Developmental factors influencing interactions of drugs. Ann N Y Acad Sci 1976; 281: 90–7PubMedCrossRef
331.
Williamson RC, Hiatt EP. Development of renal function in fetal and maternal rabbits using phenolsulfonphthalein. Proc Soc Exp Biol Med 1945; 66: 554–7
332.
Milsap RL, Szelfler SJ. Special pharmacokinetic considerations in children. In: Jusko WJ, editor. Applied pharmacokinetics: principles of therapeutic drug monitoring. Spokane (WA): Applied Therapeutics Inc., 1986: 294–330
333.
Fukuda Y, Larsson S, Celsi G, etal. Use of experimental models to study the development of renal function. Biol Neonate 1988; 53(4): 197–200PubMedCrossRef
334.
Peterson RG, Simmons MA, Rumack BH, et al. Pharmacology of furosemide in the premature newborn infant. J Pediatr 1980; 97(1): 139–43PubMedCrossRef
335.
Kelly MR, Cutler RE, Forrey AW, et al. Pharmacokinetics of orally administered furosemide. Clin Pharmacol Ther 1974; 15(2): 178–86PubMed
336.
Frenzel J, Braunlich H, Schramm D, et al. Effect on maturation of kidney function in newborn infants of repeated administration of water and electrolytes. Eur J Clin Pharmacol 1977; 11(4): 317–20PubMedCrossRef
337.
Chin JE, Soffir R, Noonan KE, et al. Structure and expression of the human MDR (P-glycoprotein) gene family. Mol Cell Biol 1989; 9(9): 3808–20PubMed
338.
Gottesman MM, Pastan I. Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu Rev Biochem 1993; 62: 385–427PubMedCrossRef
339.
Thiebaut F, Tsuruo T, Hamada H, et al. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc Natl Acad Sci U S A 1987; 84(21): 7735–8PubMedCrossRef
340.
Sugawara I, Kataoka I, Morishita Y, et al. Tissue distribution of P-glycoprotein encoded by a multidrug-resistant gene as revealed by a monoclonal antibody, MRK 16. Cancer Res 1988; 48(7): 1926–9PubMed
341.
Cordon-Cardo C, O’Brien JP, Casals D, et al. Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites. Proc Natl Acad Sci U S A 1989; 86(2): 695–8PubMedCrossRef
342.
Levine RL, Fredericks WR, Rapoport SI. Entry of bilirubin into the brain due to opening of the blood-brain barrier. Pediatrics 1982; 69(3): 255–9PubMed
343.
Roberton DM, Paganelli R, Dinwiddie R, et al. Milk antigen absorption in the preterm and term neonate. Arch Dis Child 1982; 57(5): 369–72PubMedCrossRef
344.
Borlak JT, Scott A, Henderson CJ, et al. Transfer of PCBs via lactation simultaneously induces the expression of P450 iso-enzymes and the protooncogenes c-Ha-ras and c-raf in neo-nates. Biochem Pharmacol 1996; 51(4): 517–29PubMedCrossRef
345.
Sutherland JM. Fatal cardiovascular collapse of infants receiving large amounts of chloramphenicol. Am J Dis Child 1959; 97: 761–7
346.
Bonati M, Latini R, Marra G, et al. Theophylline metabolism during the first month of life and development. Pediatr Res 1981; 15(4 Pt 1): 304–8PubMedCrossRef
347.
Gupta A, Waldhauser LK. Adverse drug reactions from birth to early childhood. Pediatr Clin North Am 1997; 44(1): 79–92PubMedCrossRef
Metadata
Title
Ontogeny of Hepatic and Renal Systemic Clearance Pathways in Infants Part I
Authors
Jane Alcorn
Dr Patrick J. McNamara
Publication date
01-10-2002
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 12/2002
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.2165/00003088-200241120-00003