Top

Published in:

01-05-2013 | Review Article

Developmental Changes in the Expression and Function of Cytochrome P450 3A Isoforms: Evidence from In Vitro and In Vivo Investigations

Authors: Ibrahim Ince, Catherijne A. J. Knibbe, Meindert Danhof, Saskia N. de Wildt

Published in: Clinical Pharmacokinetics | Issue 5/2013

Abstract

The aim of this review is to discuss our current understanding of the developmental changes of the drug-metabolizing enzyme cytochrome P450 (CYP) 3A and its impact on drug therapy. In the last 10 years, several methods have been used to study the ontogeny of specific CYP3A isoforms in vitro and in vivo. Although most studies confirm previous findings that CYP3A4/5 activity is low at birth and reaches adult values in the first years of life, there are still important gaps in our knowledge of the exact developmental patterns of individual CYP3A isoforms, especially in this age range. Moreover, most in vivo clinical studies have also failed to cover the whole pediatric age range. To date, this information gap still hampers the design of age-specific dosing guidelines of CYP3A substrate drugs, especially in neonates and infants. Innovative study methods, including opportunistic sampling and sensitive analytical assays used in combination with physiologically based pharmacokinetics, and population pharmacokinetic model concepts may help to improve our understanding of the ontogeny of CYP3A and aid the application of this knowledge in clinical practice.

Finta C, Zaphiropoulos PG. The human cytochrome P450 3A locus. Gene evolution by capture of downstream exons. Gene. 2000;260(1–2):13–23.PubMed

Domanski TL, Finta C, Halpert JR, et al. cDNA cloning and initial characterization of CYP3A43, a novel human cytochrome P450. Mol Pharmacol. 2001;59(2):386–92.PubMed

Watkins PB. Noninvasive tests of CYP3A enzymes. Pharmacogenetics. 1994;4(4):171–84.PubMed

Gellner K, Eiselt R, Hustert E, et al. Genomic organization of the human CYP3A locus: identification of a new, inducible CYP3A gene. Pharmacogenetics. 2001;11(2):111–21.PubMed

Lamba JK, Lin YS, Schuetz EG, et al. Genetic contribution to variable human CYP3A-mediated metabolism. Adv Drug Deliv Rev. 2002;54(10):1271–94.PubMed

Sim SC, Edwards RJ, Boobis AR, et al. CYP3A7 protein expression is high in a fraction of adult human livers and partially associated with the CYP3A7*1C allele. Pharmacogenet Genomics. 2005;15(9):625–31.PubMed

Guengerich FP. Cytochrome P-450 3A4: regulation and role in drug metabolism. Annu Rev Pharmacol Toxicol. 1999;39:1–17.PubMed

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):1142–51.PubMed

Kolars JC, Lown KS, Schmiedlin-Ren P, et al. CYP3A gene expression in human gut epithelium. Pharmacogenetics. 1994;4(5):247–59.PubMed

10.

Watkins PB, Wrighton SA, Schuetz EG, et al. Identification of glucocorticoid-inducible cytochromes P-450 in the intestinal mucosa of rats and man. J Clin Invest. 1987;80(4):1029–36.PubMed

11.

Westlind A, Malmebo S, Johansson I, et al. Cloning and tissue distribution of a novel human cytochrome p450 of the CYP3A subfamily, CYP3A43. Biochem Biophys Res Commun. 2001;281(5):1349–55.PubMed

12.

Vyhlidal CA, Gaedigk R, Leeder JS. Nuclear receptor expression in fetal and pediatric liver: correlation with CYP3A expression. Drug Metab Dispos. 2006;34(1):131–7.PubMed

13.

Burk O, Tegude H, Koch I, et al. Molecular mechanisms of polymorphic CYP3A7 expression in adult human liver and intestine. J Biol Chem. 2002;277(27):24280–8.PubMed

14.

Paine MF, Khalighi M, Fisher JM, et al. Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism. J Pharmacol Exp Ther. 1997;283(3):1552–62.PubMed

15.

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):515–22.PubMed

16.

Hall SD, Thummel KE, Watkins PB, et al. Molecular and physical mechanisms of first-pass extraction. Drug Metab Dispos. 1999;27(2):161–6.PubMed

17.

Ozdemir M, Crewe KH, Tucker GT, et al. Assessment of in vivo CYP2D6 activity: differential sensitivity of commonly used probes to urine pH. J Clin Pharmacol. 2004;44(12):1398–404.PubMed

18.

Elens L, Becker ML, Haufroid V, et al. Novel CYP3A4 intron 6 single nucleotide polymorphism is associated with simvastatin-mediated cholesterol reduction in The Rotterdam Study. Pharmacogenet Genomics. 2011;21(12):861–6.

19.

Elens L, van Schaik RH, Panin N, et al. Effect of a new functional CYP3A4 polymorphism on calcineurin inhibitors’ dose requirements and trough blood levels in stable renal transplant patients. Pharmacogenomics. 2011;12(10):1383–96.PubMed

20.

Lee SJ, Goldstein JA. Functionally defective or altered CYP3A4 and CYP3A5 single nucleotide polymorphisms and their detection with genotyping tests. Pharmacogenomics. 2005;6(4):357–71.PubMed

21.

Perera MA. The missing linkage: what pharmacogenetic associations are left to find in CYP3A? Expert Opin Drug Metab Toxicol. 2010;6(1):17–28.PubMed

22.

Schroder A, Klein K, Winter S, et al. Genomics of ADME gene expression: mapping expression quantitative trait loci relevant for absorption, distribution, metabolism and excretion of drugs in human liver. Pharmacogenomics J. 2013:13(1):12–20.

23.

Yang X, Zhang B, Molony C, et al. Systematic genetic and genomic analysis of cytochrome P450 enzyme activities in human liver. Genome Res. 2010;20(8):1020–36.PubMed

24.

Klein K, Thomas M, Winter S, et al. PPARA: a novel genetic determinant of CYP3A4 in vitro and in vivo. Clin Pharmacol Ther. 2012;91(6):1044–52.

25.

Gibbs MA, Thummel KE, Shen DD, et al. Inhibition of cytochrome P-450 3A (CYP3A) in human intestinal and liver microsomes: comparison of K _i values and impact of CYP3A5 expression. Drug Metab Dispos. 1999;27(2):180–7.

26.

Haehner BD, Gorski JC, Vandenbranden M, et al. Bimodal distribution of renal cytochrome P450 3A activity in humans. Mol Pharmacol. 1996;50(1):52–9.PubMed

27.

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):383–91.PubMed

28.

Maezawa K, Matsunaga T, Takezawa T, et al. Cytochrome P450 3As gene expression and testosterone 6beta-hydroxylase activity in human fetal membranes and placenta at full term. Biol Pharm Bull. 2010;33(2):249–54.PubMed

29.

van Schaik RH, van der Heiden IP, van den Anker JN, et al. CYP3A5 variant allele frequencies in Dutch Caucasians. Clin Chem. 2002;48(10):1668–71.PubMed

30.

Macphee IA, Fredericks S, Mohamed M, et al. Tacrolimus pharmacogenetics: the CYP3A5*1 allele predicts low dose-normalized tacrolimus blood concentrations in whites and South Asians. Transplantation. 2005;79(4):499–502.PubMed

31.

Zhao Y, Song M, Guan D, et al. Genetic polymorphisms of CYP3A5 genes and concentration of the cyclosporine and tacrolimus. Transpl Proc. 2005;37(1):178–81.

32.

Frohlich M, Hoffmann MM, Burhenne J, et al. Association of the CYP3A5 A6986G (CYP3A5*3) polymorphism with saquinavir pharmacokinetics. Br J Clin Pharmacol. 2004;58(4):443–4.PubMed

33.

Mouly SJ, Matheny C, Paine MF, et al. Variation in oral clearance of saquinavir is predicted by CYP3A5*1 genotype but not by enterocyte content of cytochrome P450 3A5. Clin Pharmacol Ther. 2005;78(6):605–18.PubMed

34.

Wilke RA, Moore JH, Burmester JK. Relative impact of CYP3A genotype and concomitant medication on the severity of atorvastatin-induced muscle damage. Pharmacogenet Genomics. 2005;15(6):415–21.PubMed

35.

Kivisto KT, Niemi M, Schaeffeler E, et al. Lipid-lowering response to statins is affected by CYP3A5 polymorphism. Pharmacogenetics. 2004;14(8):523–5.PubMed

36.

Inoue K, Inazawa J, Nakagawa H, et al. Assignment of the human cytochrome P-450 nifedipine oxidase gene (CYP3A4) to chromosome 7 at band q22.1 by fluorescence in situ hybridization. Jpn J Hum Genet. 1992;37(2):133–8.PubMed

37.

Komori M, Nishio K, Ohi H, et al. Molecular cloning and sequence analysis of cDNA containing the entire coding region for human fetal liver cytochrome P-450. J Biochem. 1989;105(2):161–3.PubMed

38.

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):625–34.PubMed

39.

Nishimura M, Yaguti H, Yoshitsugu H, et al. Tissue distribution of mRNA expression of human cytochrome P450 isoforms assessed by high-sensitivity real-time reverse transcription PCR. Yakugaku Zasshi. 2003;123(5):369–75.PubMed

40.

Stevens JC, Hines RN, Gu C, et al. Developmental expression of the major human hepatic CYP3A enzymes. J Pharmacol Exp Ther. 2003;307(2):573–82.PubMed

41.

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):13534–7.PubMed

42.

Leeder JS, Gaedigk R, Marcucci KA, et al. Variability of CYP3A7 expression in human fetal liver. J Pharmacol Exp Ther. 2005;314(2):626–35.PubMed

43.

Rodriguez-Antona C, Jande M, Rane A, et al. Identification and phenotype characterization of two CYP3A haplotypes causing different enzymatic capacity in fetal livers. Clin Pharmacol Ther. 2005;77(4):259–70.PubMed

44.

Daly AK. Significance of the minor cytochrome P450 3A isoforms. Clin Pharmacokinet. 2006;45(1):13–31.PubMed

45.

Ohmori S, Nakasa H, Asanome K, et al. Differential catalytic properties in metabolism of endogenous and exogenous substrates among CYP3A enzymes expressed in COS-7 cells. Biochim Biophys Acta. 1998;1380(3):297–304.PubMed

46.

de Wildt SN, Ito S, Koren G. Challenges for drug studies in children: CYP3A phenotyping as example. Drug Discov Today. 2009;14(1–2):6–15.PubMed

47.

Hakkola J, Tanaka E, Pelkonen O. Developmental expression of cytochrome P450 enzymes in human liver. Pharmacol Toxicol. 1998;82(5):209–17.PubMed

48.

Rich KJ, Boobis AR. Expression and inducibility of P450 enzymes during liver ontogeny. Microsc Res Tech. 1997;39(5):424–35.PubMed

49.

Stevens JC. New perspectives on the impact of cytochrome P450 3A expression for pediatric pharmacology. Drug Discov Today. 2006;11(9–10):440–5.PubMed

50.

Schuetz JD, Beach DL, Guzelian PS. Selective expression of cytochrome P450 CYP3A mRNAs in embryonic and adult human liver. Pharmacogenetics. 1994;4(1):11–20.PubMed

51.

Greuet J, Pichard L, Bonfils C, et al. The fetal specific gene CYP3A7 is inducible by rifampicin in adult human hepatocytes in primary culture. Biochem Biophys Res Commun. 1996;225(2):689–94.PubMed

52.

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):59–64.PubMed

53.

Pearce RE, McIntyre CJ, Madan A, et al. Effects of freezing, thawing, and storing human liver microsomes on cytochrome P450 activity. Arch Biochem Biophys. 1996;331(2):145–69.PubMed

54.

Hakkola J, Raunio H, Purkunen R, et al. Cytochrome P450 3A expression in the human fetal liver: evidence that CYP3A5 is expressed in only a limited number of fetal livers. Biol Neonate. 2001;80(3):193–201.PubMed

55.

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):207–13.PubMed

56.

Gorski JC, Hall SD, Jones DR, et al. Regioselective biotransformation of midazolam by members of the human cytochrome P450 3A (CYP3A) subfamily. Biochem Pharmacol. 1994;47(9):1643–53.PubMed

57.

Walsky RL, Obach RS, Hyland R, et al. Selective mechanism-based inactivation of CYP3A4 by CYP3cide (PF-04981517) and its utility as an in vitro tool for delineating the relative roles of CYP3A4 versus CYP3A5 in the metabolism of drugs. Drug Metab Dispos. 2012;40(9):1686–97.PubMed

58.

Yang HY, Lee QP, Rettie AE, et al. Functional cytochrome P4503A isoforms in human embryonic tissues: expression during organogenesis. Mol Pharmacol. 1994;46(5):922–8.PubMed

59.

Aleksa K, Matsell D, Krausz K, et al. Cytochrome P450 3A and 2B6 in the developing kidney: implications for ifosfamide nephrotoxicity. Pediatr Nephrol. 2005;20(7):872–85.PubMed

60.

Fakhoury M, de Beaumais T, Guimiot F, et al. mRNA expression of MDR1 and major metabolising enzymes in human fetal tissues. Drug Metab Pharmacokinet. 2009;24(6):529–36.PubMed

61.

Fakhoury M, Litalien C, Medard Y, et al. Localization and mRNA expression of CYP3A and P-glycoprotein in human duodenum as a function of age. Drug Metab Dispos. 2005;33(11):1603–7.PubMed

62.

Johnson TN, Tanner MS, Taylor CJ, et al. Enterocytic CYP3A4 in a paediatric population: developmental changes and the effect of coeliac disease and cystic fibrosis. Brit J Clin Pharmacol. 2001;51(5):451–60.

63.

Treluyer JM, Jacqz-Aigrain E, Alvarez F, et al. Expression of CYP2D6 in developing human liver. Eur J Biochem. 1991;202(2):583–8.PubMed

64.

Fukudo M, Yano I, Masuda S, et al. Population pharmacokinetic and pharmacogenomic analysis of tacrolimus in pediatric living-donor liver transplant recipients. Clin Pharmacol Ther. 2006;80(4):331–45.PubMed

65.

Fukudo M, Yano I, Yoshimura A, et al. Impact of MDR1 and CYP3A5 on the oral clearance of tacrolimus and tacrolimus-related renal dysfunction in adult living-donor liver transplant patients. Pharmacogenet Genomics. 2008;18(5):413–23.PubMed

66.

Schuetz JD, Kauma S, Guzelian PS. Identification of the fetal liver cytochrome CYP3A7 in human endometrium and placenta. J Clin Invest. 1993;92(2):1018–24.PubMed

67.

Kirwan C, MacPhee I, Philips B. Using drug probes to monitor hepatic drug metabolism in critically ill patients: midazolam, a flawed but useful tool for clinical investigation of CYP3A activity? Expert Opin Drug Metab Toxicol. 2010;6(6):761–71.PubMed

68.

Kashuba AD, Nafziger AN, Kearns GL, et al. Limitations of dextromethorphan N-demethylation as a measure of CYP3A activity. Pharmacogenetics. 1999;9(4):453–62.PubMed

69.

Lowry JA, Kearns GL, Abdel-Rahman SM, et al. Cisapride: a potential model substrate to assess cytochrome P4503A4 activity in vivo. Clin Pharmacol Ther. 2003;73(3):209–22.PubMed

70.

de Wildt SN, Kearns GL, Hop WC, et al. Pharmacokinetics and metabolism of intravenous midazolam in preterm infants. Clin Pharmacol Ther. 2001;70(6):525–31.PubMed

71.

de Wildt SN, de Hoog M, Vinks AA, et al. Population pharmacokinetics and metabolism of midazolam in pediatric intensive care patients. Crit Care Med. 2003;31(7):1952–8.PubMed

72.

Allegaert K, Van den Anker JN, Debeer A, et al. Maturational changes in the in vivo activity of CYP3A4 in the first months of life. Int J Clin Pharmacol Ther. 2006;44(7):303–8.PubMed

73.

Blake MJ, Abdel-Rahman SM, Pearce RE, et al. Effect of diet on the development of drug metabolism by cytochrome P-450 enzymes in healthy infants. Pediatr Res. 2006;60(6):717–23.PubMed

74.

de Wildt SN, Berns MJ, van den Anker JN. 13C-erythromycin breath test as a noninvasive measure of CYP3A activity in newborn infants: a pilot study. Ther Drug Monit. 2007;29(2):225–30.PubMed

75.

de Wildt SN, Kearns GL, Hop WC, et al. Pharmacokinetics and metabolism of oral midazolam in preterm infants. Br J Clin Pharmacol. 2002;53(4):390–2.PubMed

76.

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):414–23.PubMed

77.

Thummel KE, Shen DD, Podoll TD, et al. Use of midazolam as a human cytochrome P450 3A probe: I. In vitro–in vivo correlations in liver transplant patients. J Pharmacol Exp Ther. 1994;271(1):549–56.

78.

Wang RW, Newton DJ, Liu NY, et al. Inhibitory anti-CYP3A4 peptide antibody: mapping of inhibitory epitope and specificity toward other CYP3A isoforms. Drug Metab Dispos. 1999;27(2):167–72.PubMed

79.

Burtin P, Jacqz-Aigrain E, Girard P, et al. Population pharmacokinetics of midazolam in neonates. Clin Pharmacol Ther. 1994;56(6 Pt 1):615–25.PubMed

80.

Jacqz-Aigrain E, Wood C, Robieux I. Pharmacokinetics of midazolam in critically ill neonates. Eur J Clin Pharmacol. 1990;39(2):191–2.PubMed

81.

Jacqz-Aigrain E, Daoud P, Burtin P, et al. Pharmacokinetics of midazolam during continuous infusion in critically ill neonates. Eur J Clin Pharmacol. 1992;42(3):329–32.PubMed

82.

Williams JA, Ring BJ, Cantrell VE, et al. Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7. Drug Metab Dispos. 2002;30(8):883–91.PubMed

83.

Rey E, Delaunay L, Pons G, et al. Pharmacokinetics of midazolam in children: comparative study of intranasal and intravenous administration. Eur J Clin Pharmacol. 1991;41(4):355–7.PubMed

84.

Reed MD, Rodarte A, Blumer JL, et al. The single-dose pharmacokinetics of midazolam and its primary metabolite in pediatric patients after oral and intravenous administration. J Clin Pharmacol. 2001;41(12):1359–69.PubMed

85.

Jones RD, Chan K, Roulson CJ, et al. Pharmacokinetics of flumazenil and midazolam. Br J Anaesth. 1993;70(3):286–92.PubMed

86.

Tolia V, Brennan S, Aravind MK, et al. Pharmacokinetic and pharmacodynamic study of midazolam in children during esophagogastroduodenoscopy. J Pediatr. 1991;119(3):467–71.PubMed

87.

Hartwig S, Roth B, Theisohn M. Clinical experience with continuous intravenous sedation using midazolam and fentanyl in the paediatric intensive care unit. Eur J Pediatr. 1991;150(11):784–8.PubMed

88.

Peeters MY, Prins SA, Knibbe CA, et al. Propofol pharmacokinetics and pharmacodynamics for depth of sedation in nonventilated infants after major craniofacial surgery. Anesthesiology. 2006;104(3):466–74.PubMed

89.

Peeters MY, Prins SA, Knibbe CA, et al. Pharmacokinetics and pharmacodynamics of midazolam and metabolites in nonventilated infants after craniofacial surgery. Anesthesiology. 2006;105(6):1135–46.PubMed

90.

Greenblatt DJ, Ehrenberg BL, Gunderman J, et al. Pharmacokinetic and electroencephalographic study of intravenous diazepam, midazolam, and placebo. Clin Pharmacol Ther. 1989;45(4):356–65.PubMed

91.

Mandema JW, Tuk B, van Steveninck AL, et al. Pharmacokinetic-pharmacodynamic modeling of the central nervous system effects of midazolam and its main metabolite alpha-hydroxymidazolam in healthy volunteers. Clin Pharmacol Ther. 1992;51(6):715–28.PubMed

92.

Anderson BJ, Larsson P. A maturation model for midazolam clearance. Paediatr Anaesth. 2011;21(3):302–8.PubMed

93.

Vet NJ, de Hoog M, Tibboel D, et al. The effect of critical illness and inflammation on midazolam therapy in children. Pediatr Crit Care Med. 2012;13(1):e48–50.

94.

Hughes J, Gill AM, Mulhearn H, et al. Steady-state plasma concentrations of midazolam in critically ill infants and children. Ann Pharmacother. 1996;30(1):27–30.PubMed

95.

Mathews HM, Carson IW, Lyons SM, et al. A pharmacokinetic study of midazolam in paediatric patients undergoing cardiac surgery. Br J Anaesth. 1988;61(3):302–7.PubMed

96.

Fromm MF, Busse D, Kroemer HK, et al. Differential induction of prehepatic and hepatic metabolism of verapamil by rifampin. Hepatology. 1996;24(4):796–801.PubMed

97.

Hebert MF, Roberts JP, Prueksaritanont T, et al. Bioavailability of cyclosporine with concomitant rifampin administration is markedly less than predicted by hepatic enzyme induction. Clin Pharmacol Ther. 1992;52(5):453–7.PubMed

98.

Holtbecker N, Fromm MF, Kroemer HK, et al. The nifedipine–rifampin interaction. Evidence for induction of gut wall metabolism. Drug Metab Dispos. 1996;24(10):1121–3.

99.

Thummel KE, O’Shea D, Paine MF, et al. Oral first-pass elimination of midazolam involves both gastrointestinal and hepatic CYP3A-mediated metabolism. Clin Pharmacol Ther. 1996;59(5):491–502.PubMed

100.

Wu CY, Benet LZ, Hebert MF, et al. Differentiation of absorption and first-pass gut and hepatic metabolism in humans: studies with cyclosporine. Clin Pharmacol Ther. 1995;58(5):492–7.PubMed

101.

Lown KS, Ghosh M, Watkins PB. Sequences of intestinal and hepatic cytochrome P450 3A4 cDNAs are identical. Drug Metab Dispos. 1998;26(2):185–7.PubMed

102.

Smith MT, Eadie MJ, Brophy TO. The pharmacokinetics of midazolam in man. Eur J Clin Pharmacol. 1981;19(4):271–8.PubMed

103.

Marshall J, Rodarte A, Blumer J, et al. Pediatric pharmacodynamics of midazolam oral syrup. Pediatric Pharmacology Research Unit Network. J Clin Pharmacol. 2000;40(6):578–89.PubMed

104.

Maclennan S, Augood C, Cash-Gibson L, et al. Cisapride treatment for gastro-oesophageal reflux in children. Cochrane Database Syst Rev. 2010(4):CD002300.

105.

Preechagoon Y, Charles B, Piotrovskij V, et al. Population pharmacokinetics of enterally administered cisapride in young infants with gastro-oesophageal reflux disease. Brit J Clin Pharmacol. 1999;48(5):688–93.

106.

Kearns GL, Robinson PK, Wilson JT, et al. Cisapride disposition in neonates and infants: in vivo reflection of cytochrome P450 3A4 ontogeny. Clin Pharmacol Ther. 2003;74(4):312–25.PubMed

107.

Blake MJ, Gaedigk A, Pearce RE, et al. Ontogeny of dextromethorphan O- and N-demethylation in the first year of life. Clin Pharmacol Ther. 2007;81(4):510–6.PubMed

108.

Johnson TN, Tucker GT, Rostami-Hodjegan A. Development of CYP2D6 and CYP3A4 in the first year of life. Clin Pharmacol Ther. 2008;83(5):670–1.PubMed

109.

Rostami-Hodjegan A, Kroemer HK, Tucker GT. In-vivo indices of enzyme activity: the effect of renal impairment on the assessment of CYP2D6 activity. Pharmacogenetics. 1999;9(3):277–86.PubMed

110.

Johnson TN, Thomson M. Intestinal metabolism and transport of drugs in children: the effects of age and disease. J Pediatric Gastroenterol Nutr. 2008;47(1):3–10.

111.

Ferraresso M, Tirelli A, Ghio L, et al. Influence of the CYP3A5 genotype on tacrolimus pharmacokinetics and pharmacodynamics in young kidney transplant recipients. Pediatr Transpl. 2007;11(3):296–300.

112.

de Wildt SN, van Schaik RH, Soldin OP, et al. The interactions of age, genetics, and disease severity on tacrolimus dosing requirements after pediatric kidney and liver transplantation. Eur J Clin Pharmacol. 2011.

113.

Gijsen V, Mital S, van Schaik RH, et al. Age and CYP3A5 genotype affect tacrolimus dosing requirements after transplant in pediatric heart recipients. J Heart Lung Transpl. 2011;30(12):1352–9.

114.

Zhao W, Elie V, Roussey G, et al. Population pharmacokinetics and pharmacogenetics of tacrolimus in de novo pediatric kidney transplant recipients. Clin Pharmacol Ther. 2009;86(6):609–18.PubMed

115.

Terrazzino S, Quaglia M, Stratta P, et al. The effect of CYP3A5 6986A>G and ABCB1 3435C>T on tacrolimus dose-adjusted trough levels and acute rejection rates in renal transplant patients: a systematic review and meta-analysis. Pharmacogenet Genomics. 2012;22(8):642–5.

116.

Drocourt L, Ourlin JC, Pascussi JM, et al. Expression of CYP3A4, CYP2B6, and CYP2C9 is regulated by the vitamin D receptor pathway in primary human hepatocytes. J Biol Chem. 2002;277(28):25125–32.PubMed

117.

Gibson GG, Plant NJ, Swales KE, et al. Receptor-dependent transcriptional activation of cytochrome P4503A genes: induction mechanisms, species differences and interindividual variation in man. Xenobiotica. 2002;32(3):165–206.PubMed

118.

Goodwin B, Redinbo MR, Kliewer SA. Regulation of cyp3a gene transcription by the pregnane x receptor. Annu Rev Pharmacol Toxicol. 2002;42:1–23.PubMed

119.

Pascussi JM, Gerbal-Chaloin S, Drocourt L, et al. The expression of CYP2B6, CYP2C9 and CYP3A4 genes: a tangle of networks of nuclear and steroid receptors. Biochim Biophys Acta. 2003;1619(3):243–53.PubMed

120.

Chartier FL, Bossu JP, Laudet V, et al. Cloning and sequencing of cDNAs encoding the human hepatocyte nuclear factor 4 indicate the presence of two isoforms in human liver. Gene. 1994;147(2):269–72.PubMed

121.

Tirona RG, Lee W, Leake BF, et al. The orphan nuclear receptor HNF4alpha determines PXR- and CAR-mediated xenobiotic induction of CYP3A4. Nat Med. 2003;9(2):220–4.PubMed

122.

Gerbal-Chaloin S, Daujat M, Pascussi JM, et al. Transcriptional regulation of CYP2C9 gene. Role of glucocorticoid receptor and constitutive androstane receptor. J Biol Chem. 2002;277(1):209–17.PubMed

123.

Kacevska M, Ivanov M, Wyss A, et al. DNA methylation dynamics in the hepatic CYP3A4 gene promoter. Biochimie. 2012;94(11):2338–44.

124.

Goodwin B, Hodgson E, D’Costa DJ, et al. Transcriptional regulation of the human CYP3A4 gene by the constitutive androstane receptor. Mol Pharmacol. 2002;62(2):359–65.PubMed

125.

Goodwin B, Hodgson E, Liddle C. The orphan human pregnane X receptor mediates the transcriptional activation of CYP3A4 by rifampicin through a distal enhancer module. Mol Pharmacol. 1999;56(6):1329–39.PubMed

126.

Hines RN. Ontogeny of human hepatic cytochromes P450. J Biochem Mol Toxicol. 2007;21(4):169–75.PubMed

127.

Payne K, Mattheyse FJ, Liebenberg D, et al. The pharmacokinetics of midazolam in paediatric patients. Eur J Clin Pharmacol. 1989;37(3):267–72.PubMed

128.

Ince I, de Wildt SN, Peeters MY, et al. Critical illness is a major determinant of midazolam clearance in children aged 1 month to 17 years. Ther Drug Monit. 2012;34(4):381–9.

129.

Vet NJ, de Hoog M, Tibboel D, et al. The effect of inflammation on drug metabolism: a focus on pediatrics. Drug Discov Today. 2011;16(9–10):435–42.PubMed

130.

Carcillo JA, Doughty L, Kofos D, et al. Cytochrome P450 mediated-drug metabolism is reduced in children with sepsis-induced multiple organ failure. Intensive Care Med. 2003;29(6):980–4.PubMed

131.

Kearns GL, Abdel-Rahman SM, Alander SW, et al. Developmental pharmacology—drug disposition, action, and therapy in infants and children. N Engl J Med. 2003;349(12):1157–67.PubMed

132.

Björkman S. Prediction of cytochrome p450-mediated hepatic drug clearance in neonates, infants and children: how accurate are available scaling methods? Clin Pharmacokinet. 2006;45(1):1–11.PubMed

133.

Edginton AN, Schmitt W, Voith B, et al. A mechanistic approach for the scaling of clearance in children. Clin Pharmacokinet. 2006;45(7):683–704.PubMed

134.

Johnson TN, Rostami-Hodjegan A, Tucker GT. Prediction of the clearance of eleven drugs and associated variability in neonates, infants and children. Clin Pharmacokinet. 2006;45(9):931–56.PubMed

135.

Ince I, de Wildt SN, Tibboel D, et al. Tailor-made drug treatment for children: creation of an infrastructure for data-sharing and population PK-PD modeling. Drug Discov Today. 2009;14(5–6):316–20.PubMed

136.

Krekels EHJ, Johnson TN, den Hoedt SM, et al. Top–down modeling meets bottom–up modeling: the physiological and physicochemical basis for the ontogeny of UGT2B7-mediated drug glucuronidation. 2012. http://www.page-meeting.org/?abstract=2369.

137.

Leong R, Vieira ML, Zhao P, et al. Regulatory experience with physiologically based pharmacokinetic modeling for pediatric drug trials. Clin Pharmacol Ther. 2012;91(5):926–31.PubMed

138.

Schaefer O, Ohtsuki S, Kawakami H, et al. Absolute quantification and differential expression of drug transporters, cytochrome P450 enzymes, and UDP-glucuronosyltransferases in cultured primary human hepatocytes. Drug Metab Dispos. 2012;40(1):93–103.PubMed

139.

Muchohi SN, Kokwaro GO, Ogutu BR, et al. Pharmacokinetics and clinical efficacy of midazolam in children with severe malaria and convulsions. Br J Clin Pharmacol. 2008;66(4):529–38.PubMed

Title: Developmental Changes in the Expression and Function of Cytochrome P450 3A Isoforms: Evidence from In Vitro and In Vivo Investigations
Authors: Ibrahim Ince
Catherijne A. J. Knibbe
Meindert Danhof
Saskia N. de Wildt
Publication date: 01-05-2013
Publisher: Springer International Publishing AG
Published in: Clinical Pharmacokinetics / Issue 5/2013
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI: https://doi.org/10.1007/s40262-013-0041-1

At a glance: The STEP trials

Springer Medicine

Developmental Changes in the Expression and Function of Cytochrome P450 3A Isoforms: Evidence from In Vitro and In Vivo Investigations

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 5/2013

Population Pharmacokinetics of Metformin in Healthy Subjects and Patients with Type 2 Diabetes Mellitus: Simulation of Doses According to Renal Function

Quantifying the Effect of Covariates on Concentrations and Effects of Steady-State Phenprocoumon Using a Population Pharmacokinetic/Pharmacodynamic Model

Single-Center Evaluation of the Single-Dose Pharmacokinetics of the Angiotensin II Receptor Antagonist Azilsartan Medoxomil in Renal Impairment

Letter to the Editor: Pharmacokinetics of Non-Intravenous Formulations of Fentanyl

Clinical Pharmacokinetics and Pharmacodynamics of Mycophenolate in Patients with Autoimmune Disease

Pharmacokinetics of Intravenous Conivaptan in Subjects With Hepatic or Renal Impairment