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 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 5/2012

01-05-2012 | Review Article

Impact of Obesity on Drug Metabolism and Elimination in Adults and Children

Authors: Margreke J. E. Brill, Jeroen Diepstraten, Anne van Rongen, Simone van Kralingen, John N. van den Anker, Professor Catherijne A. J. Knibbe

Published in: Clinical Pharmacokinetics | Issue 5/2012

Login to get access

Abstract

The prevalence of obesity in adults and children is rapidly increasing across the world. Several general (patho)physiological alterations associated with obesity have been described, but the specific impact of these alterations on drug metabolism and elimination and its consequences for drug dosing remains largely unknown.
In order to broaden our knowledge of this area, we have reviewed and summarized clinical studies that reported clearance values of drugs in both obese and non-obese patients. Studies were classified according to their most important metabolic or elimination pathway. This resulted in a structured review of the impact of obesity on metabolic and elimination processes, including phase I metabolism, phase II metabolism, liver blood flow, glomerular filtration and tubular processes.
This literature study shows that the influence of obesity on drug metabolism and elimination greatly differs per specific metabolic or elimination pathway. Clearance of cytochrome P450 (CYP) 3A4 substrates is lower in obese as compared with non-obese patients. In contrast, clearance of drugs primarily metabolized by uridine diphosphate glucuronosyltransferase (UGT), glomerular filtration and/or tubular-mediated mechanisms, xanthine oxidase, N-acetyltransferase or CYP2E1 appears higher in obese versus non-obese patients. Additionally, in obese patients, trends indicating higher clearance values were seen for drugs metabolized via CYP1A2, CYP2C9, CYP2C19 and CYP2D6, while studies on high-extraction-ratio drugs showed somewhat inconclusive results. Very limited information is available in obese children, which prevents a direct comparison between data obtained in obese children and obese adults.
Future clinical studies, especially in children, adolescents and morbidly obese individuals, are needed to extend our knowledge in this clinically important area of adult and paediatric clinical pharmacology.
Literature
1.
2.
Flegal KM, Carroll MD, Ogden CL, et al. Prevalence and trends in obesity among US adults, 1999–2008. JAMA 2010 Jan 20; 303(3): 235–41PubMedCrossRef
3.
Ogden CL, Carroll MD, Curtin LR, et al. Prevalence of overweight and obesity in the United States, 1999–2004. JAMA 2006 Apr 5; 295(13): 1549–55PubMedCrossRef
4.
5.
Ogden CL, Carroll MD, Curtin LR, et al. Prevalence of high body mass index in US children and adolescents, 2007–2008. JAMA 2010 Jan 20; 303(3): 242–9PubMedCrossRef
6.
Jia WP, Wang C, Jiang S, et al. Characteristics of obesity and its related disorders in China. Biomed Environ Sci 2010 Feb; 23(1): 4–11PubMedCrossRef
7.
Kelly T, Yang W, Chen CS, et al. Global burden of obesity in 2005 and projections to 2030. Int J Obes (Lond) 2008 Sep; 32(9): 1431–7CrossRef
8.
Cheymol G. Clinical pharmacokinetics of drugs in obesity: an update. Clin Pharmacokinet 1993 Aug; 25(2): 103–14PubMedCrossRef
9.
Cheymol G. Effects of obesity on pharmacokinetics implications for drug therapy. Clin Pharmacokinet 2000 Sep; 39(3): 215–31PubMedCrossRef
10.
Alexander JK, Dennis EW, Smith WG, et al. Blood volume, cardiac output, and distribution of systemic blood flow in extreme obesity. Cardiovasc Res Cent Bull 1962 Winter; 1: 39–44PubMed
11.
Zavorsky GS. Cardiopulmonary aspects of obesity in women. Obstet Gynecol Clin North Am 2009 Jun; 36(2): 267–84, viiiPubMedCrossRef
12.
Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Invest 2005 May; 115(5): 1111–9PubMed
13.
Guzzaloni G, Grugni G, Minocci A, et al. Liver steatosis in juvenile obesity: correlations with lipid profile, hepatic biochemical parameters and glycemic and insulinemic responses to an oral glucose tolerance test. Int J Obes Relat Metab Disord 2000 Jun; 24(6): 772–6PubMedCrossRef
14.
Wree A, Kahraman A, Gerken G, et al. Obesity affects the liver: the link between adipocytes and hepatocytes. Digestion 2011; 83(1–2): 124–33PubMedCrossRef
15.
Fisher CD, Lickteig AJ, Augustine LM, et al. Hepatic cytochrome P450 enzyme alterations in humans with progressive stages of nonalcoholic fatty liver disease. Drug Metab Dispos 2009 Oct; 37(10): 2087–94PubMedCrossRef
16.
Donato MT, Lahoz A, Jimenez N, et al. Potential impact of steatosis on cytochrome P450 enzymes of human hepatocytes isolated from fatty liver grafts. Drug Metab Dispos 2006 Sep; 34(9): 1556–62PubMedCrossRef
17.
Donato MT, Jimenez N, Serralta A, et al. Effects of steatosis on drug-metabolizing capability of primary human hepatocytes. Toxicol In Vitro 2007 Mar; 21(2): 271–6PubMedCrossRef
18.
Emery MG, Fisher JM, Chien JY, et al. CYP2E1 activity before and after weight loss in morbidly obese subjects with nonalcoholic fatty liver disease. Hepatology 2003 Aug; 38(2): 428–35PubMedCrossRef
19.
Casati A, Putzu M. Anesthesia in the obese patient: pharmacokinetic considerations. J Clin Anesth 2005 Mar; 17(2): 134–45PubMedCrossRef
20.
21.
Darbari DS, Neely M, van den Anker J, et al. Increased clearance of morphine in sickle cell disease: implications for pain management. J Pain 2011 May; 12(5): 531–8PubMedCrossRef
22.
Jain R, Chung SM, Jain L, et al. Implications of obesity for drug therapy: limitations and challenges. Clin Pharmacol Ther 2011 Jul; 90(1): 77–89PubMedCrossRef
23.
Abernethy DR, Greenblatt DJ. Drug disposition in obese humans: an update. Clin Pharmacokinet 1986 May–Jun; 11(3): 199–213PubMedCrossRef
24.
Mulla H, Johnson TN. Dosing dilemmas in obese children. Arch Dis Child Educ Pract Ed 2010 Aug; 95(4): 112–7PubMedCrossRef
25.
Hanley MJ, Abernethy DR, Greenblatt DJ. Effect of obesity on the pharmacokinetics of drugs in humans. Clin Pharmacokinet 2010; 49(2): 71–87PubMedCrossRef
26.
Ingrande J, Lemmens HJ. Dose adjustment of anaesthetics in the morbidly obese. Br J Anaesth 2010; 105 Suppl. 1: i16–23PubMedCrossRef
27.
Morrish GA, Pai MP, Green B. The effects of obesity on drug pharmacokinetics in humans. Expert Opin Drug Metab Toxicol 2011 Jun; 7(6): 697–706PubMedCrossRef
28.
Abernethy DR, Greenblatt DJ. Pharmacokinetics of drugs in obesity. Clin Pharmacokinet 1982 Mar–Apr; 7(2): 108–24PubMedCrossRef
29.
Kotlyar M, Carson SW. Effects of obesity on the cytochrome P450 enzyme system. Int J Clin Pharmacol Ther 1999 Jan; 37(1): 8–19PubMed
30.
Edelman AB, Cherala G, Stanczyk FZ. Metabolism and pharmacokinetics of contraceptive steroids in obese women: a review. Contraception 2010 Oct; 82(4): 314–23PubMedCrossRef
31.
Green B, Duffull SB. What is the best size descriptor to use for pharmacokinetic studies in the obese? Br J Clin Pharmacol 2004 Aug; 58(2): 119–33PubMedCrossRef
32.
33.
Williams RT. Detoxication mechanisms: the metabolism and detoxication of drugs,toxic substances, and other organic compounds. 2nd ed. London: Chapman and Hall, 1959
34.
Moretto M, Kupski C, Mottin CC, et al. Hepatic steatosis in patients undergoing bariatric surgery and its relationship to body mass index and comorbidities. Obes Surg 2003 Aug; 13(4): 622–4PubMedCrossRef
35.
Silverman JF, O’Brien KF, Long S, et al. Liver pathology in morbidly obese patients with and without diabetes. Am J Gastroenterol 1990 Oct; 85(10): 1349–55PubMed
36.
Harnois F, Msika S, Sabate JM, et al. Prevalence and predictive factors of non-alcoholic steatohepatitis (NASH) in morbidly obese patients undergoing bariatric surgery. Obes Surg 2006 Feb; 16(2): 183–8PubMedCrossRef
37.
Thorn M, Finnstrom N, Lundgren S, et al. Cytochromes P450 and MDR1 mRNA expression along the human gastrointestinal tract. Br J Clin Pharmacol 2005 Jul; 60(1): 54–60PubMedCrossRef
38.
Lindell M, Karlsson MO, Lennernas H, et al. Variable expression of CYP and Pgp genes in the human small intestine. Eur J Clin Invest 2003 Jun; 33(6): 493–9PubMedCrossRef
39.
40.
Evans WE, Relling MV. Pharmacogenomics: translating functional genomics into rational therapeutics. Science 1999 Oct 15; 286(5439): 487–91PubMedCrossRef
41.
Reddy VB, Doss GA, Karanam BV, et al. In vitro and in vivo metabolism of a novel cannabinoid-1 receptor inverse agonist, taranabant, in rats and monkeys. Xenobiotica 2010 Sep; 40(9): 650–62PubMedCrossRef
42.
Li XS, Nielsen J, Cirincione B, et al. Development of a population pharmacokinetic model for taranabant, a cannibinoid-1 receptor inverse agonist. AAPS J 2010 Dec; 12(4): 537–47PubMedCrossRef
43.
Koolen SL, Oostendorp RL, Beijnen JH, et al. Population pharmacokinetics of intravenously and orally administered docetaxel with or without co-administration of ritonavir in patients with advanced cancer. Br J Clin Pharmacol 2010 May; 69(5): 465–74PubMedCrossRef
44.
Sparreboom A, Wolff AC, Mathijssen RH, et al. Evaluation of alternate size descriptors for dose calculation of anticancer drugs in the obese. J Clin Oncol 2007 Oct 20; 25(30): 4707–13PubMedCrossRef
45.
Kerr BM, Thummel KE, Wurden CJ, et al. Human liver carbamazepine metabolism: role of CYP3A4 and CYP2C8 in 10,11-epoxide formation. Biochem Pharmacol 1994 Jun 1; 47(11): 1969–79PubMedCrossRef
46.
Caraco Y, Zylber-Katz E, Berry EM, et al. Carbamazepine pharmacokinetics in obese and lean subjects. Ann Pharmacother 1995 Sep; 29(9): 843–7PubMed
47.
Caraco Y, Zylber-Katz E, Berry EM, et al. Significant weight reduction in obese subjects enhances carbamazepine elimination. Clin Pharmacol Ther 1992 May; 51(5): 501–6PubMedCrossRef
48.
Watkins PB. The role of cytochromes P-450 in cyclosporine metabolism. J Am Acad Dermatol 1990 Dec; 23(6 Pt 2): 1301–9; discussion 1309-11PubMedCrossRef
49.
Hunt CM, Westerkam WR, Stave GM, et al. Hepatic cytochrome P-4503A (CYP3A) activity in the elderly. Mech Ageing Dev 1992 Jun; 64(1–2): 189–99PubMedCrossRef
50.
Hunt CM, Watkins PB, Saenger P, et al. Heterogeneity of CYP3A isoforms metabolizing erythromycin and cortisol. Clin Pharmacol Ther 1992 Jan; 51(1): 18–23PubMedCrossRef
51.
Streetman DS, Bertino Jr JS, Nafziger AN. Phenotyping of drug-metabolizing enzymes in adults: a review of in-vivo cytochrome P450 phenotyping probes. Pharmacogenetics 2000 Apr; 10(3): 187–216PubMedCrossRef
52.
Greenblatt DJ, Abernethy DR, Locniskar A, et al. Effect of age, gender, and obesity on midazolam kinetics. Anesthesiology 1984 Jul; 61(1): 27–35PubMed
53.
Ohno Y, Hisaka A, Suzuki H. General framework for the quantitative prediction of CYP3A4-mediated oral drug interactions based on the AUC increase by coadministration of standard drugs. Clin Pharmacokinet 2007; 46(8): 681–96PubMedCrossRef
54.
Abernethy DR, Greenblatt DJ, Divoll M, et al. The influence of obesity on the pharmacokinetics of oral alprazolam and triazolam. Clin Pharmacokinet 1984 Mar–Apr; 9(2): 177–83PubMedCrossRef
55.
Flechner SM, Kolbeinsson ME, Tam J, et al. The impact of body weight on cyclosporine pharmacokinetics in renal transplant recipients. Transplantation 1989 May; 47(5): 806–10PubMedCrossRef
56.
Yee GC, Lennon TP, Gmur DJ, et al. Effect of obesity on cyclosporine disposition. Transplantation 1988 Mar; 45(3): 649–51PubMedCrossRef
57.
Rotzinger S, Fang J, Baker GB. Trazodone is metabolized to m-chlorophenylpiperazine by CYP3A4 from human sources. Drug Metab Dispos 1998 Jun; 26(6): 572–5PubMed
58.
Mihara K, Otani K, Suzuki A, et al. Relationship between the CYP2D6 genotype and the steady-state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine. Psychopharmacology (Berl) 1997 Sep; 133(1): 95–8CrossRef
59.
Greenblatt DJ, Friedman H, Burstein ES, et al. Trazodone kinetics: effect of age, gender, and obesity. Clin Pharmacol Ther 1987 Aug; 42(2): 193–200PubMedCrossRef
60.
Kharasch ED, Russell M, Mautz D, et al. The role of cytochrome P450 3A4 in alfentanil clearance: implications for interindividual variability in disposition and perioperative drug interactions. Anesthesiology 1997 Jul; 87(1): 36–50PubMedCrossRef
61.
Bentley J, Finley J, Humphrey L, et al. Obesity and alfentanil pharmacokinetics [abstract]. Anesth Analg 1983; 62: 251
62.
Marterre WF, Hariharan S, First MR, et al. Gastric bypass in morbidly obese kidney transplant recipients. Clin Transplant 1996 Oct; 10(5): 414–9PubMed
63.
Boni J, Leister C, Burns J, et al. Pharmacokinetic profile of temsirolimus with concomitant administration of cytochrome p450-inducing medications. J Clin Pharmacol 2007 Nov; 47(11): 1430–9PubMedCrossRef
64.
Kamdem LK, Streit F, Zanger UM, et al. Contribution of CYP3A5 to the in vitro hepatic clearance of tacrolimus. Clin Chem 2005 Aug; 51(8): 1374–81PubMedCrossRef
65.
Picard N, Cresteil T, Premaud A, et al. Characterization of a phase 1 metabolite of mycophenolic acid produced by CYP3A4/5. Ther Drug Monit 2004 Dec; 26(6): 600–8PubMedCrossRef
66.
Rogers CC, Alloway RR, Alexander JW, et al. Pharmacokinetics of mycophenolic acid, tacrolimus and sirolimus after gastric bypass surgery in endstage renal disease and transplant patients: a pilot study. Clin Transplant 2008 May–Jun; 22(3): 281–91PubMedCrossRef
67.
Skottheim IB, Jakobsen GS, Stormark K, et al. Significant increase in systemic exposure of atorvastatin after biliopancreatic diversion with duodenal switch. Clin Pharmacol Ther 2010 Jun; 87(6): 699–705PubMedCrossRef
68.
Skottheim IB, Stormark K, Christensen H, et al. Significantly altered systemic exposure to atorvastatin acid following gastric bypass surgery in morbidly obese patients. Clin Pharmacol Ther 2009 Sep; 86(3): 311–8PubMedCrossRef
69.
Lucas D, Ferrara R, Gonzalez E, et al. Chlorzoxazone, a selective probe for phenotyping CYP2E1 in humans. Pharmacogenetics 1999 Jun; 9(3): 377–88PubMedCrossRef
70.
Lucas D, Farez C, Bardou LG, et al. Cytochrome P450 2E1 activity in diabetic and obese patients as assessed by chlorzoxazone hydroxylation. Fundam Clin Pharmacol 1998; 12(5): 553–8PubMedCrossRef
71.
O’Shea D, Davis SN, Kim RB, et al. Effect of fasting and obesity in humans on the 6-hydroxylation of chlorzoxazone: a putative probe of CYP2E1 activity. Clin Pharmacol Ther 1994 Oct; 56(4): 359–67PubMedCrossRef
72.
Kharasch ED, Thummel KE, Mautz D, et al. Clinical enflurane metabolism by cytochrome P450 2E1. Clin Pharmacol Ther 1994 Apr; 55(4): 434–40PubMedCrossRef
73.
Miller MS, Gandolfi AJ, Vaughan RW, et al. Disposition of enflurane in obese patients. J Pharmacol Exp Ther 1980 Nov; 215(2): 292–6PubMed
74.
Bentley JB, Vaughan RW, Miller MS, et al. Serum inorganic fluoride levels in obese patients during and after enflurane anesthesia. Anesth Analg 1979 Sep–Oct; 58(5): 409–12PubMedCrossRef
75.
76.
Higuchi H, Satoh T, Arimura S, et al. Serum inorganic fluoride levels in mildly obese patients during and after sevoflurane anesthesia. Anesth Analg 1993 Nov; 77(5): 1018–21PubMedCrossRef
77.
Frink Jr EJ, Malan Jr TP, Brown EA, et al. Plasma inorganic fluoride levels with sevoflurane anesthesia in morbidly obese and nonobese patients. Anesth Analg 1993 Jun; 76(6): 1333–7PubMed
78.
Reichle FM, Conzen PF. Halogenated inhalational anaesthetics. Best Pract Res Clin Anaesthesiol 2003 Mar; 17(1): 29–46PubMedCrossRef
79.
Bentley JB, Vaughan RW, Gandolfi AJ, et al. Halothane biotransformation in obese and nonobese patients. Anesthesiology 1982 Aug; 57(2): 94–7PubMedCrossRef
80.
Barshop NJ, Capparelli EV, Sirlin CB, et al. Acetaminophen pharmacokinetics in children with nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr 2011 Feb; 52(2): 198–202PubMedCrossRef
81.
Abernethy DR, Divoll M, Greenblatt DJ, et al. Obesity, sex, and acetaminophen disposition. Clin Pharmacol Ther 1982 Jun; 31(6): 783–90PubMedCrossRef
82.
Rumack BH. Acetaminophen hepatotoxicity: the first 35 years. J Toxicol Clin Toxicol 2002; 40(1): 3–20PubMedCrossRef
83.
84.
85.
Haritos VS, Ching MS, Ghabrial H, et al. Metabolism of dexfenfluramine in human liver microsomes and by recombinant enzymes: role of CYP2D6 and 1A2. Pharmacogenetics 1998 Oct; 8(5): 423–32PubMedCrossRef
86.
Cheymol G, Weissenburger J, Poirier JM, et al. The pharmacokinetics of dexfenfluramine in obese and non-obese subjects. Br J Clin Pharmacol 1995 Jun; 39(6): 684–7PubMed
87.
Lefebvre J, Poirier L, Poirier P, et al. The influence of CYP2D6 phenotype on the clinical response of nebivolol in patients with essential hypertension. Br J Clin Pharmacol 2007 May; 63(5): 575–82PubMedCrossRef
88.
Cheymol G, Woestenborghs R, Snoeck E, et al. Pharmacokinetic study and cardiovascular monitoring of nebivolol in normal and obese subjects. Eur J Clin Pharmacol 1997; 51(6): 493–8PubMedCrossRef
89.
Schrenk D, Brockmeier D, Morike K, et al. A distribution study of CYP1A2 phenotypes among smokers and non-smokers in a cohort of healthy Caucasian volunteers. Eur J Clin Pharmacol 1998 Jan; 53(5): 361–7PubMedCrossRef
90.
Rostami-Hodjegan A, Nurminen S, Jackson PR, et al. Caffeine urinary metabolite ratios as markers of enzyme activity: a theoretical assessment. Pharmacogenetics 1996 Apr; 6(2): 121–49PubMedCrossRef
91.
Rasmussen BB, Brosen K. Theophylline has no advantages over caffeine as a putative model drug for assessing CYPIA2 activity in humans. Br J Clin Pharmacol 1997 Mar; 43(3): 253–8PubMedCrossRef
92.
Chine MS, Schwarzenberg SJ, Johnson LA. Altered xanthine oxidase and N-acetyl transferase activity in obese children. Br J Clin Pharmacol 2011 Jul; 72(1): 109–15CrossRef
93.
Caraco Y, Zylber-Katz E, Berry EM, et al. Caffeine pharmacokinetics in obesity and following significant weight reduction. Int J Obes Relat Metab Disord 1995 Apr; 19(4): 234–9PubMed
94.
Kamimori GH, Somani SM, Knowlton RG, et al. The effects of obesity and exercise on the pharmacokinetics of caffeine in lean and obese volunteers. Eur J Clin Pharmacol 1987; 31(5): 595–600PubMedCrossRef
95.
Abernethy DR, Todd EL, Schwartz JB. Caffeine disposition in obesity. Br J Clin Pharmacol 1985 Jul; 20(1): 61–6PubMedCrossRef
96.
Zahorska-Markiewicz B, Waluga M, Zielinski M, et al. Pharmacokinetics of theophylline in obesity. Int J Clin Pharmacol Ther 1996 Sep; 34(9): 393–5PubMed
97.
Jusko WJ, Gardner MJ, Mangione A, et al. Factors affecting theophylline clearances: age, tobacco, marijuana, cirrhosis, congestive heart failure, obesity, oral contraceptives, benzodiazepines, barbiturates, and ethanol. J Pharm Sci 1979 Nov; 68(11): 1358–66PubMedCrossRef
98.
Blouin RA, Elgert JF, Bauer LA. Theophylline clearance: effect of marked obesity. Clin Pharmacol Ther 1980 Nov; 28(5): 619–23PubMedCrossRef
99.
Langtry HD, Balfour JA. Glimepiride: a review of its use in the management of type 2 diabetes mellitus. Drugs 1998 Apr; 55(4): 563–84PubMedCrossRef
100.
Shukla UA, Chi EM, Lehr KH. Glimepiride pharmacokinetics in obese versus non-obese diabetic patients. Ann Pharmacother 2004 Jan; 38(1): 30–5PubMedCrossRef
101.
Tan B, Zhang YF, Chen XY, et al. The effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of glipizide in Chinese subjects. Eur J Clin Pharmacol 2010 Feb; 66(2): 145–51PubMedCrossRef
102.
Jaber LA, Ducharme MP, Halapy H. The effects of obesity on the pharmacokinetics and pharmacodynamics of glipizide in patients with non-insulin-dependent diabetes mellitus. Ther Drug Monit 1996 Feb; 18(1): 6–13PubMedCrossRef
103.
Garcia-Martin E, Martinez C, Tabares B, et al. Interindividual variability in ibuprofen pharmacokinetics is related to interaction of cytochrome P450 2C8 and 2C9 amino acid polymorphisms. Clin Pharmacol Ther 2004 Aug; 76(2): 119–27PubMedCrossRef
104.
Abernethy DR, Greenblatt DJ. Ibuprofen disposition in obese individuals. Arthritis Rheum 1985 Oct; 28(10): 1117–21PubMedCrossRef
105.
Kumar V, Wahlstrom JL, Rock DA, et al. CYP2C9 inhibition: impact of probe selection and pharmacogenetics on in vitro inhibition profiles. Drug Metab Dispos 2006 Dec; 34(12): 1966–75PubMedCrossRef
106.
Abernethy DR, Greenblatt DJ. Phenytoin disposition in obesity: determination of loading dose. Arch Neurol 1985 May; 42(5): 468–71PubMedCrossRef
107.
Gonzalez FJ, Idle JR. Pharmacogenetic phenotyping and genotyping: present status and future potential. Clin Pharmacokinet 1994; 26(1): 59–70PubMedCrossRef
108.
He SM, Zhou ZW, Li XT, et al. Clinical drugs undergoing polymorphic metabolism by human cytochrome P450 2C9 and the implication in drug development. Curr Med Chem 2011; 18(5): 667–713PubMedCrossRef
109.
Flockhart DA. Drug interactions and the cytochrome P450 system: the role of cytochrome P450 2C19. Clin Pharmacokinet 1995; 29 Suppl. 1: 45–52PubMedCrossRef
110.
Bertilsson L, Henthorn TK, Sanz E, et al. Importance of genetic factors in the regulation of diazepam metabolism: relationship to S-mephenytoin, but not debrisoquin, hydroxylation phenotype. Clin Pharmacol Ther 1989 Apr; 45(4): 348–55PubMedCrossRef
111.
Abernethy DR, Greenblatt DJ, Divoll M, et al. Alterations in drug distribution and clearance due to obesity. J Pharmacol Exp Ther 1981 Jun; 217(3): 681–5PubMed
112.
Abernethy DR, Greenblatt DJ, Divoll M, et al. Prolongation of drug half-life due to obesity: studies of desmethyldiazepam (clorazepate). J Pharm Sci 1982 Aug; 71(8): 942–4PubMedCrossRef
113.
Strolin Benedetti M, Whomsley R, Baltes E. Involvement of enzymes other than CYPs in the oxidative metabolism of xenobiotics. Expert Opin Drug Metab Toxicol 2006 Dec; 2(6): 895–921PubMedCrossRef
114.
Balis FM. Pharmacokinetic drug interactions of commonly used anticancer drugs. Clin Pharmacokinet 1986 May–Jun; 11(3): 223–35PubMedCrossRef
115.
Zuccaro P, Guandalini S, Pacifici R, et al. Fat body mass and pharmacokinetics of oral 6-mercaptopurine in children with acute lymphoblastic leukemia. Ther Drug Monit 1991 Jan; 13(1): 37–41PubMedCrossRef
116.
Yanni SB, Annaert PP, Augustijns P, et al. In vitro hepatic metabolism explains higher clearance of voriconazole in children versus adults: role of CYP2C19 and flavin-containing monooxygenase 3. Drug Metab Dispos 2010 Jan; 38(1): 25–31PubMedCrossRef
117.
Pai MP, Lodise TP. Steady-state plasma pharmacokinetics of oral voriconazole in obese adults. Antimicrob Agents Chemother 2011 Jun; 55(6): 2601–5PubMedCrossRef
118.
Ebner T, Remmel RP, Burchell B. Human bilirubin UDP-glucuronosyltransferase catalyzes the glucuronidation of ethinylestradiol. Mol Pharmacol 1993 Apr; 43(4): 649–54PubMed
119.
Palovaara S, Tybring G, Laine K. The effect of ethinyloestradiol and levonorgestrel on the CYP2C19-mediated metabolism of omeprazole in healthy female subjects. Br J Clin Pharmacol 2003 Aug; 56(2): 232–7PubMedCrossRef
120.
Yamazaki H, Shaw PM, Guengerich FP, et al. Roles of cytochromes P450 1A2 and 3A4 in the oxidation of estradiol and estrone in human liver microsomes. Chem Res Toxicol 1998 Jun; 11(6): 659–65PubMedCrossRef
121.
Westhoff CL, Torgal AH, Mayeda ER, et al. Pharmacokinetics of a combined oral contraceptive in obese and normal-weight women. Contraception 2010 Jun; 81(6): 474–80PubMedCrossRef
122.
Stanczyk FZ, Roy S. Metabolism of levonorgestrel, norethindrone, and structurally related contraceptive steroids. Contraception 1990 Jul; 42(1): 67–96PubMedCrossRef
123.
Edelman A, Munar M, Elman MR, et al. Effect of ethinyl estradiol/levonorgestrel combined oral contraceptive on the activity of cytochrome P4503A in obese women. Br J Clin Pharmacol. Epub 2012 Feb 2
124.
Ohyama K, Nakajima M, Nakamura S, et al. A significant role of human cytochrome P450 2C8 in amiodarone N-deethylation: an approach to predict the contribution with relative activity factor. Drug Metab Dispos 2000 Nov; 28(11): 1303–10PubMed
125.
Fukuchi H, Nakashima M, Araki R, et al. Effect of obesity on serum amiodarone concentration in Japanese patients: population pharmacokinetic investigation by multiple trough screen analysis. J Clin Pharm Ther 2009 Jun; 34(3): 329–36PubMedCrossRef
126.
Brain EG, Yu LJ, Gustafsson K, et al. Modulation of P450-dependent ifosfamide pharmacokinetics: a better understanding of drug activation in vivo. Br J Cancer 1998 Jun; 77(11): 1768–76PubMedCrossRef
127.
Lind MJ, Margison JM, Cerny T, et al. Prolongation of ifosfamide elimination half-life in obese patients due to altered drug distribution. Cancer Chemother Pharmacol 1989; 25(2): 139–42PubMedCrossRef
128.
Engel G, Hofmann U, Heidemann H, et al. Antipyrine as a probe for human oxidative drug metabolism: identification of the cytochrome P450 enzymes catalyzing 4-hydroxyantipyrine, 3-hydroxymethylantipyrine, and norantipyrine formation. Clin Pharmacol Ther 1996 Jun; 59(6): 613–23PubMedCrossRef
129.
Walter-Sack I, Klotz U. Influence of diet and nutritional status on drug metabolism. Clin Pharmacokinet 1996 Jul; 31(1): 47–64PubMedCrossRef
130.
Caraco Y, Zylber-Katz E, Berry EM, et al. Antipyrine disposition in obesity: evidence for negligible effect of obesity on hepatic oxidative metabolism. Eur J Clin Pharmacol 1995; 47(6): 525–30PubMedCrossRef
131.
Horikiri Y, Suzuki T, Mizobe M. Pharmacokinetics and metabolism of bisoprolol enantiomers in humans. J Pharm Sci 1998 Mar; 87(3): 289–94PubMedCrossRef
132.
Le Jeunne C, Poirier JM, Cheymol G, et al. Pharmacokinetics of intravenous bisoprolol in obese and non-obese volunteers. Eur J Clin Pharmacol 1991; 41(2): 171–4PubMedCrossRef
133.
Krishna S, White NJ. Pharmacokinetics of quinine, chloroquine and amodiaquine: clinical implications. Clin Pharmacokinet 1996 Apr; 30(4): 263–99PubMedCrossRef
134.
Viriyayudhakorn S, Thitiarchakul S, Nachaisit S, et al. Pharmacokinetics of quinine in obesity. Trans R Soc Trop Med Hyg 2000 Jul–Aug; 94(4): 425–8PubMedCrossRef
135.
Zharikova OL, Fokina VM, Nanovskaya TN, et al. Identification of the major human hepatic and placental enzymes responsible for the bio-transformation of glyburide. Biochem Pharmacol 2009 Dec 15; 78(12): 1483–90PubMedCrossRef
136.
Jaber LA, Antal EJ, Slaughter RL, et al. The pharmacokinetics and pharmacodynamics of 12 weeks of glyburide therapy in obese diabetics. Eur J Clin Pharmacol 1993; 45(5): 459–63PubMedCrossRef
137.
Joerger M, Huitema AD, Meenhorst PL, et al. Pharmacokinetics of low-dose doxorubicin and metabolites in patients with AIDS-related Kaposi sarcoma. Cancer Chemother Pharmacol 2005 May; 55(5): 488–96PubMedCrossRef
138.
Rudek MA, Sparreboom A, Garrett-Mayer ES, et al. Factors affecting pharmacokinetic variability following doxorubicin and docetaxel-based therapy. Eur J Cancer 2004 May; 40(8): 1170–8PubMedCrossRef
139.
Thompson PA, Rosner GL, Matthay KK, et al. Impact of body composition on pharmacokinetics of doxorubicin in children: a Glaser Pediatric Research Network study. Cancer Chemother Pharmacol 2009 Jul; 64(2): 243–51PubMedCrossRef
140.
Kiang TK, Ensom MH, Chang TK. UDP-glucuronosyltransferases and clinical drug-drug interactions. Pharmacol Ther 2005 Apr; 106(1): 97–132PubMedCrossRef
141.
Tchernof A, Levesque E, Beaulieu M, et al. Expression of the androgen metabolizing enzyme UGT2B15 in adipose tissue and relative expression measurement using a competitive RT-PCR method. Clin Endocrinol (Oxf) 1999 May; 50(5): 637–42CrossRef
142.
Mutlib AE, Goosen TC, Bauman JN, et al. Kinetics of acetaminophen glucuronidation by UDP-glucuronosyltransferases 1A1, 1A6, 1A9 and 2B15: potential implications in acetaminophen-induced hepatotoxicity. Chem Res Toxicol 2006 May; 19(5): 701–9PubMedCrossRef
143.
Hayakawa H, Fukushima Y, Kato H, et al. Metabolism and disposition of novel des-fluoro quinolone garenoxacin in experimental animals and an interspecies scaling of pharmacokinetic parameters. Drug Metab Dispos 2003 Nov; 31(11): 1409–18PubMedCrossRef
144.
Van Wart S, Phillips L, Ludwig EA, et al. Population pharmacokinetics and pharmacodynamics of garenoxacin in patients with community-acquired respiratory tract infections. Antimicrob Agents Chemother 2004 Dec; 48(12): 4766–77PubMedCrossRef
145.
Court MH, Duan SX, Guillemette C, et al. Stereoselective conjugation of oxazepam by human UDP-glucuronosyltransferases (UGTs): S-oxazepam is glucuronidated by UGT2B15, while R-oxazepam is glucuronidated by UGT2B7 and UGT1A9. Drug Metab Dispos 2002 Nov; 30(11): 1257–65PubMedCrossRef
146.
Abernethy DR, Greenblatt DJ, Divoll M, et al. Enhanced glucuronide conjugation of drugs in obesity: studies of lorazepam, oxazepam, and acetaminophen. J Lab Clin Med 1983 Jun; 101(6): 873–80PubMed
147.
Chung JY, Cho JY, Yu KS, et al. Effect of the UGT2B15 genotype on the pharmacokinetics, pharmacodynamics, and drug interactions of intravenous lorazepam in healthy volunteers. Clin Pharmacol Ther 2005 Jun; 77(6): 486–94PubMedCrossRef
148.
Okumura K, Kita T, Chikazawa S, et al. Genotyping of N-acetylation polymorphism and correlation with procainamide metabolism. Clin Pharmacol Ther 1997 May; 61(5): 509–17PubMedCrossRef
149.
Christoff PB, Conti DR, Naylor C, et al. Procainamide disposition in obesity. Drug Intell Clin Pharm 1983 Jul–Aug; 17(7–8): 516–22PubMed
150.
Czerwinski M, Gibbs JP, Slattery JT. Busulfan conjugation by glutathione S-transferases alpha, mu, and pi. Drug Metab Dispos 1996 Sep; 24(9): 1015–9PubMed
151.
Browning B, Thormann K, Donaldson A, et al. Busulfan dosing in children with BMIs ≥85% undergoing HSCT: a new optimal strategy. Biol Blood Marrow Transplant 2011 Sep; 17(9): 1383–8PubMedCrossRef
152.
Nguyen L, Leger F, Lennon S, et al. Intravenous busulfan in adults prior to haematopoietic stem cell transplantation: a population pharmacokinetic study. Cancer Chemother Pharmacol 2006 Jan; 57(2): 191–8PubMedCrossRef
153.
Gibbs JP, Gooley T, Corneau B, et al. The impact of obesity and disease on busulfan oral clearance in adults. Blood 1999 Jun 15; 93(12): 4436–40PubMed
154.
Buggia I, Zecca M, Alessandrino EP, et al. Itraconazole can increase systemic exposure to busulfan in patients given bone marrow transplantation. GITMO (Gruppo Italiano Trapianto di Midollo Osseo). Anticancer Res 1996 Jul–Aug; 16(4A): 2083–8PubMed
155.
Farrell GC, Teoh NC, McCuskey RS. Hepatic microcirculation in fatty liver disease. Anat Rec (Hoboken) 2008 Jun; 291(6): 684–92CrossRef
156.
Al-Jahdari WS, Yamamoto K, Hiraoka H, et al. Prediction of total propofol clearance based on enzyme activities in microsomes from human kidney and liver. Eur J Clin Pharmacol 2006 Jul; 62(7): 527–33PubMedCrossRef
157.
van Kralingen S, Diepstraten J, Peeters MYM, et al. Population pharmacokinetics and pharmacodynamics of propofol in morbidly obese patients. Clin Pharmacokinet 2011 Nov 1; 50(11): 739–50PubMedCrossRef
158.
Cortinez LI, Anderson BJ, Penna A, et al. Influence of obesity on propofol pharmacokinetics: derivation of a pharmacokinetic model. Br J Anaesth 2010 Oct; 105(4): 448–56PubMedCrossRef
159.
Rahman A, Korzekwa KR, Grogan J, et al. Selective biotransformation of taxol to 6 alpha-hydroxytaxol by human cytochrome P450 2C8. Cancer Res 1994 Nov 1; 54(21): 5543–6PubMed
160.
Tateishi T, Krivoruk Y, Ueng YF, et al. Identification of human liver cytochrome P-450 3A4 as the enzyme responsible for fentanyl and sufentanil N-dealkylation. Anesth Analg 1996 Jan; 82(1): 167–72PubMed
161.
Gepts E, Shafer SL, Camu F, et al. Linearity of pharmacokinetics and model estimation of sufentanil. Anesthesiology 1995 Dec; 83(6): 1194–204PubMedCrossRef
162.
Schwartz AE, Matteo RS, Ornstein E, et al. Pharmacokinetics of sufentanil in obese patients. Anesth Analg 1991 Dec; 73(6): 790–3PubMed
163.
Masubuchi Y, Hosokawa S, Horie T, et al. Cytochrome P450 isozymes involved in propranolol metabolism in human liver microsomes: the role of CYP2D6 as ring-hydroxylase and CYP1A2 as N-desisopropylase. Drug Metab Dispos 1994 Nov–Dec; 22(6): 909–15PubMed
164.
Wojcicki J, Jaroszynska M, Drozdzik M, et al. Comparative pharmacokinetics and pharmacodynamics of propranolol and atenolol in normolipaemic and hyperlipidaemic obese subjects. Biopharm Drug Dispos 2003 Jul; 24(5): 211–8PubMedCrossRef
165.
Cheymol G, Poirier JM, Carrupt PA, et al. Pharmacokinetics of beta-adrenoceptor blockers in obese and normal volunteers. Br J Clin Pharmacol 1997 Jun; 43(6): 563–70PubMedCrossRef
166.
Cheymol G, Poirier JM, Barre J, et al. Comparative pharmacokinetics of intravenous propranolol in obese and normal volunteers. J Clin Pharmacol 1987 Nov; 27(11): 874–9PubMedCrossRef
167.
Bowman SL, Hudson SA, Simpson G, et al. A comparison of the pharmacokinetics of propranolol in obese and normal volunteers. Br J Clin Pharmacol 1986 May; 21(5): 529–32PubMedCrossRef
168.
McNeil JJ, Louis WJ. Clinical pharmacokinetics of labetalol. Clin Pharmacokinet 1984 Mar–Apr; 9(2): 157–67PubMedCrossRef
169.
Hamann SR, Blouin RA, McAllister Jr RG, et al. Clinical pharmacokinetics of verapamil. Clin Pharmacokinet 1984 Jan–Feb; 9(1): 26–41PubMedCrossRef
170.
Echizen H, Eichelbaum M. Clinical pharmacokinetics of verapamil, nifedipine and diltiazem. Clin Pharmacokinet 1986 Nov–Dec; 11(6): 425–49PubMedCrossRef
171.
Abernethy DR, Schwartz JB. Verapamil pharmacodynamics and disposition in obese hypertensive patients. J Cardiovasc Pharmacol 1988 Feb; 11(2): 209–15PubMed
172.
Zito RA, Reid PR. Lidocaine kinetics predicted by indocyanine green clearance. N Engl J Med 1978 May 25; 298(21): 1160–3PubMedCrossRef
173.
Abernethy DR, Greenblatt DJ. Lidocaine disposition in obesity. Am J Cardiol 1984 Apr 1; 53(8): 1183–6PubMedCrossRef
174.
Oda Y, Mizutani K, Hase I, et al. Fentanyl inhibits metabolism of midazolam: competitive inhibition of CYP3A4 in vitro. Br J Anaesth 1999 Jun; 82(6): 900–3PubMedCrossRef
175.
Shibutani K, Inchiosa Jr MA, Sawada K, et al. Accuracy of pharmacokinetic models for predicting plasma fentanyl concentrations in lean and obese surgical patients: derivation of dosing weight (“pharmacokinetic mass”). Anesthesiology 2004 Sep; 101(3): 603–13PubMedCrossRef
176.
Routledge PA, Shand DG. Clinical pharmacokinetics of propranolol. Clin Pharmacokinet 1979 Mar–Apr; 4(2): 73–90PubMedCrossRef
177.
Pea F, Licari M, Baldassarre M, et al. MEGX disposition in critically-ill trauma patients: subsequent assessments during the first week following trauma. Fundam Clin Pharmacol 2002 Dec; 16(6): 519–25PubMedCrossRef
178.
Koska 3rd AJ, Romagnoli A, Kramer WG. Effect of cardiopulmonary bypass on fentanyl distribution and elimination. Clin Pharmacol Ther 1981 Jan; 29(1): 100–5PubMedCrossRef
179.
Jiko M, Yano I, Okuda M, et al. Altered pharmacokinetics of paclitaxel in experimental hepatic or renal failure. Pharm Res 2005 Feb; 22(2): 228–34PubMedCrossRef
180.
Pai MP. Estimating the glomerular filtration rate in obese adult patients for drug dosing. Adv Chronic Kidney Dis 2010 Sep; 17(5): e53–62PubMedCrossRef
181.
Ribstein J, du Cailar G, Mimran A. Combined renal effects of overweight and hypertension. Hypertension 1995 Oct; 26(4): 610–5PubMedCrossRef
182.
183.
Kasiske BL, Crosson JT. Renal disease in patients with massive obesity. Arch Intern Med 1986 Jun; 146(6): 1105–9PubMedCrossRef
184.
Cindik N, Baskin E, Agras PI, et al. Effect of obesity on inflammatory markers and renal functions. Acta Paediatr 2005 Dec; 94(12): 1732–7PubMedCrossRef
185.
Csernus K, Lanyi E, Erhardt E, et al. Effect of childhood obesity and obesity-related cardiovascular risk factors on glomerular and tubular protein excretion. Eur J Pediatr 2005 Jan; 164(1): 44–9PubMedCrossRef
186.
Savino A, Pelliccia P, Giannini C, et al. Implications for kidney disease in obese children and adolescents. Pediatr Nephrol 2011 May; 26(5): 749–58PubMedCrossRef
187.
Post FA, Wyatt CM, Mocroft A. Biomarkers of impaired renal function. Curr Opin HIV AIDS 2010 Nov; 5(6): 524–30PubMedCrossRef
188.
Henegar JR, Bigler SA, Henegar LK, et al. Functional and structural changes in the kidney in the early stages of obesity. J Am Soc Nephrol 2001 Jun; 12(6): 1211–7PubMed
189.
Matzke GR, Zhanel GG, Guay DR. Clinical pharmacokinetics of vancomycin. Clin Pharmacokinet 1986 Jul–Aug; 11(4): 257–82PubMedCrossRef
190.
Bauer LA, Black DJ, Lill JS. Vancomycin dosing in morbidly obese patients. Eur J Clin Pharmacol 1998 Oct; 54(8): 621–5PubMedCrossRef
191.
Dvorchik B, Arbeit RD, Chung J, et al. Population pharmacokinetics of daptomycin. Antimicrob Agents Chemother 2004 Aug; 48(8): 2799–807PubMedCrossRef
192.
Pai MP, Norenberg JP, Anderson T, et al. Influence of morbid obesity on the single-dose pharmacokinetics of daptomycin. Antimicrob Agents Chemother 2007 Aug; 51(8): 2741–7PubMedCrossRef
193.
Dvorchik BH, Damphousse D. The pharmacokinetics of daptomycin in moderately obese, morbidly obese, and matched nonobese subjects. J Clin Pharmacol 2005 Jan; 45(1): 48–56PubMedCrossRef
194.
Harland SJ, Newell DR, Siddik ZH, et al. Pharmacokinetics of cis-diammine-1,1-cyclobutane dicarboxylate platinum(II) in patients with normal and impaired renal function. Cancer Res 1984 Apr; 44(4): 1693–7PubMed
195.
Ekhart C, Rodenhuis S, Schellens JH, et al. Carboplatin dosing in overweight and obese patients with normal renal function, does weight matter? Cancer Chemother Pharmacol 2009 Jun; 64(1): 115–22PubMedCrossRef
196.
Schmitt A, Gladieff L, Lansiaux A, et al. A universal formula based on cystatin C to perform individual dosing of carboplatin in normal weight, underweight, and obese patients. Clin Cancer Res 2009 May 15; 15(10): 3633–9PubMedCrossRef
197.
Frydman A. Low-molecular-weight heparins: an overview of their pharmacodynamics, pharmacokinetics and metabolism in humans. Haemostasis 1996; 26 Suppl. 2: 24–38PubMed
198.
Barras MA, Duffull SB, Atherton JJ, et al. Modelling the occurrence and severity of enoxaparin-induced bleeding and bruising events. Br J Clin Pharmacol 2009 Nov; 68(5): 700–11PubMedCrossRef
199.
Yee JY, Duffull SB. The effect of body weight on dalteparin pharmacokinetics: a preliminary study. Eur J Clin Pharmacol 2000 Jul; 56(4): 293–7PubMedCrossRef
200.
Barrett JS, Gibiansky E, Hull RD, et al. Population pharmacodynamics in patients receiving tinzaparin for the prevention and treatment of deep vein thrombosis. Int J Clin Pharmacol Ther 2001 Oct; 39(10): 431–46PubMed
201.
Richards DA. Comparative pharmacodynamics and pharmacokinetics of cimetidine and ranitidine. J Clin Gastroenterol 1983; 5 Suppl. 1: 81–90PubMedCrossRef
202.
Abernethy DR, Greenblatt DJ, Matlis R, et al. Cimetidine disposition in obesity. Am J Gastroenterol 1984 Feb; 79(2): 91–4PubMed
203.
Lewis TV, Johnson PN, Nebbia AM, et al. Increased enoxaparin dosing is required for obese children. Pediatrics 2011 Mar; 127(3): e787–90PubMedCrossRef
204.
Karlsson E. Clinical pharmacokinetics of procainamide. Clin Pharmacokinet 1978 Mar–Apr; 3(2): 97–107PubMedCrossRef
205.
Drusano GL. An overview of the pharmacology of intravenously administered ciprofloxacin. Am J Med 1987 Apr 27; 82(4A): 339–45PubMed
206.
Allard S, Kinzig M, Boivin G, et al. Intravenous ciprofloxacin disposition in obesity. Clin Pharmacol Ther 1993 Oct; 54(4): 368–73PubMedCrossRef
207.
Daley-Yates PT, McBrien DC. The mechanism of renal clearance of cisplatin (cis-dichlorodiammine platinum II) and its modification by furosemide and probenecid. Biochem Pharmacol 1982 Jul 1; 31(13): 2243–6PubMedCrossRef
208.
Zamboni WC, Houghton PJ, Johnson RK, et al. Probenecid alters topotecan systemic and renal disposition by inhibiting renal tubular secretion. J Pharmacol Exp Ther 1998 Jan; 284(1): 89–94PubMed
209.
210.
Abernethy DR, Greenblatt DJ, Smith TW. Digoxin disposition in obesity: clinical pharmacokinetic investigation. Am Heart J 1981 Oct; 102(4): 740–4PubMedCrossRef
211.
212.
Reiss RA, Haas CE, Karki SD, et al. Lithium pharmacokinetics in the obese. Clin Pharmacol Ther 1994 Apr; 55(4): 392–8PubMedCrossRef
213.
Chagnac A, Herman M, Zingerman B, et al. Obesity-induced glomerular hyperfiltration: its involvement in the pathogenesis of tubular sodium reabsorption. Nephrol Dial Transplant 2008 Dec; 23(12): 3946–52PubMedCrossRef
214.
Mortensen A, Lenz K, Abildstrom H, et al. Anesthetizing the obese child. Paediatr Anaesth 2011 Jun; 21(6): 623–9PubMedCrossRef
Metadata
Title
Impact of Obesity on Drug Metabolism and Elimination in Adults and Children
Authors
Margreke J. E. Brill
Jeroen Diepstraten
Anne van Rongen
Simone van Kralingen
John N. van den Anker
Professor Catherijne A. J. Knibbe
Publication date
01-05-2012
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 5/2012
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.2165/11599410-000000000-00000