Chapter 18
Predicting Interindividual Variability of Metabolic Drug–Drug Interactions: Identifying the Causes and Accounting for Them Using a Systems Approach
Amin Rostami-Hodjegan,
Amin Rostami-Hodjegan
Department of Systems Pharmacology The Medical School, University of Sheffield, United Kingdom
Search for more papers by this authorAmin Rostami-Hodjegan,
Amin Rostami-Hodjegan
Department of Systems Pharmacology The Medical School, University of Sheffield, United Kingdom
Search for more papers by this authorBook Editor(s):Chuang Lu,
Albert P. Li,
Chuang Lu
Department of DMPK, Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts, USA
Search for more papers by this authorAlbert P. Li
In Vitro ADMET Laboratories, Columbia, Maryland, USA
Search for more papers by this authorSummary
This chapter contains sections titled:
-
Introduction
-
Pharmacokinetic Building Blocks Determining M-DDI
-
Current Knowledge of ADME Variability Relevant to M-DDI
-
Tools for Incorporating Interindividual Variability in M-DDI
-
Conclusions
-
References
REFERENCES
- Aithal GP, Day CP, Kesteven PJ, Daly AK. Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet 1999; 353: 717–719.
- Almond LM, Yang J, Jamei M, Tucker GT, Rostami-Hodjegan A. Towards a quantitative framework for the prediction of DDI's arising from Cytochrome P450 induction. Curr Drug Metab 2009; 10: 420–432.
- Berthou F, Goasduff T, Lucas D, Dreano Y, Le Bot MH, Menez JF. Interaction between two probes used for phenotyping cytochromes P4501A2 (caffeine) and P4502E1 (chlorzoxazone) in humans. Pharmacogenetics 1995; 5: 72–79.
- Boddy AV, Cole M, Pearson AD, Idle JR. The kinetics of the auto-induction of ifosfamide metabolism during continuous infusion. Cancer Chemother Pharmacol 1995; 36: 53–60.
- Chu V, Einolf HJ, Evers R, Kumar G, Moore D, Ripp S, Silva J, Sinha V, Sinz M, Skerjanec A. In vitro and in vivo induction of cytochrome p450: a survey of the current practices and recommendations: a Pharmaceutical Research and Manufacturers of America perspective. Drug Metab Dispos 2009; 37: 1339–1547.
- Collins C, Levy R, Ragueneau-Majlessi I, Hachad H. Prediction of maximum exposure in poor metabolizers following inhibition of nonpolymorphic pathways. Curr Drug Metab 2006; 7: 295–299.
- Diaz D, Fabre I, Daujat M, Saint Aubert B, Bories P, Michel H, Maurel P. Omeprazole is an aryl hydrocarbon-like inducer of human hepatic cytochrome P450. Gastroenterology 1990; 99: 737–747.
- Dickinson GL, Lennard MS, Tucker GT, Rostami-Hodjegan A. The use of mechanistic DM-PK-PD modelling to assess the power of pharmacogenetic studies—CYP2C9 and warfarin as an example. Br J Clin Pharmacol 2007; 64: 14–26
- Dressman JB, Fleisher D. Mixing-tank model for predicting dissolution rate control or oral absorption. J Pharm Sci 1986; 75: 109–116.
- Dressman JB, Berardi RR, Dermentzoglou LC, Russell TL, Schmaltz SP, Barnett JL, Jarvenpaa KM. Upper gastrointestinal (GI) pH in young, healthy men and women. Pharm Res 1990; 7: 756–761.
- Einolf HJ. Comparison of different approaches to predict metabolic drug—drug interactions. Xenobiotica 2007; 37: 1257–1294.
- Emery MG, Jubert C, Thummel KE, Kharasch ED. Duration of cytochrome P-450 2E1 (CYP2E1) inhibition and estimation of functional CYP2E1 enzyme half-life after single-dose disulfiram administration in humans. J Pharmacol Exp Ther 1999; 291: 213–219.
- Evans DF, Pye G, Bramley R, Clark AG, Dyson TJ, Hardcastle JD. Measurement of gastrointestinal pH profiles in normal ambulant human subjects. Gut 1988; 29: 1035–1041.
- Faber MS, Fuhr U. Time response of cytochrome P450 1A2 activity on cessation of heavy smoking. Clin Pharmacol Ther 2004; 76: 178–184.
- Fahmi OA, Hurst S, Plowchalk D, Cook J, Guo F, Youdim K, Dickins M, Phipps A, Darekar A, Hyland R, Obach RS. Comparison of different algorithms for predicting clinical drug-drug interactions, based on the use of CYP3A4 in vitro data: predictions of compounds as precipitants of interaction. Drug Metab Dispos 2009; 37: 1658–1666.
- Fromm MF, Busse D, Kroemer HK, Eichelbaum M. Differential induction of prehepatic and hepatic metabolism of verapamil by rifampin. Hepatology 1996; 24: 796–801.
- Ghanbari F, Rowland-Yeo K, Bloomer JC, Clarke SE, Lennard MS, Tucker GT, Rostami-Hodjegan A. A critical evaluation of the experimental design of studies of mechanism based enzyme inhibition, with implications for in vitro—in vivo extrapolation. Curr Drug Metab 2006; 7: 315–334.
- Grimm SW, Einolf HJ, Hall SD, He K, Lim HK, Ling KH, Lu C, Nomeir AA, Seibert E, Skordos KW, Tonn GR, Van Horn R, Wang RW, Wong YN, Yang TJ, Obach RS. The conduct of in vitro studies to address time-dependent inhibition of drug-metabolizing enzymes: a perspective of the pharmaceutical research and manufacturers of America. Drug Metab Dispos 2009; 37: 1355–1370.
- Higashi MK, Veenstra DL, Kondo LM, Wittkowsky AK, Srinouanprachanh SL, Farin FM, Rettie AE. Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy. Jama 2002; 287: 1690–1698.
- Hsu A, Granneman GR, Witt G, Locke C, Denissen J, Molla A, Valdes J, Smith J, Erdman K, Lyons N, Niu P, Decourt JP, Fourtillan JB, Girault J, Leonard JM. Multiple-dose pharmacokinetics of ritonavir in human immunodeficiency virus-infected subjects. Antimicrob Agents Chemother 1997; 41: 898–905.
- Jamei M, Dickinson GL, Rostami-Hodjegan A. A framework for assessing interindividual variability in pharmacokinetics using virtual human populations and integrating general knowledge of physical chemistry, biology, anatomy, physiology and genetics: a tale of “bottom-up” vs “top-down” recognition of covariates. Drug Metab Pharmacokin 2009a; 24: 53–75.
- Jamei M, Marciniak S, Feng K, Barnett A, Tucker GT, Rostami-Hodjegan A. The Simcyp® population-based ADME simulator. Expert Opin Drug Metab Toxicol 2009b; 5: 211–223.
- Jamei M, Turner D, Yang J, Neuhoff S, Polak S, Rostami-Hodjegan A, Tucker GT. Population-based mechanistic prediction of oral drug absorption. AAPS Journal 2009c; 11: 225–237.
- Kamali F, Khan TI, King BP, Frearson R, Kesteven P, Wood P, Daly AK, Wynne H. Contribution of age, body size, and CYP2C9 genotype to anticoagulant response to warfarin. Clin Pharmacol Ther 2004; 75: 204–212.
- Kolars JC, Schmiedlin-Ren P, Schuetz JD, Fang C, Watkins PB. Identification of rifampin-inducible P450IIIA4 (CYP3A4) in human small bowel enterocytes. J Clin Invest 1992; 90: 1871–1878.
- Krayenbuhl JC, Vozeh S, Kondo-Oestreicher M, Dayer P. Drug—drug interactions of new active substances: mibefradil example. Eur J Clin Pharmacol 1999; 55: 559–565.
- Lai AA, Levy RH, Cutler RE. Time-course of interaction between carbamazepine and clonazepam in normal man. Clin Pharmacol Ther 1978; 24: 316–323.
- Lalonde RL, Kowalski KG, Hutmacher MM, Ewy W, Nichols DJ, Milligan PA, Corrigan BW, Lockwood PA, Marshall SA, Benincosa LJ, Tensfeldt TG, Parivar K, Amantea M, Glue P, Koide H, Miller R. Model-based drug development. Clin Pharmacol Ther 2007; 82: 21–32.
- Lin JH, Chiba M, Baillie TA. In vivo assessment of intestinal drug metabolism. Drug Metab Dispos 1997; 25: 1107–1109.
- Liston HL, DeVane CL, Boulton DW, Risch SC, Markowitz JS, Goldman J. Differential time course of cytochrome P450 2D6 enzyme inhibition by fluoxetine, sertraline, and paroxetine in healthy volunteers. J Clin Psychopharmacol 2002; 22: 169–173.
- Loebstein R, Yonath H, Peleg D, Almog S, Rotenberg M, Lubetsky A, Roitelman J, Harats D, Halkin H, Ezra D. Interindividual variability in sensitivity to warfarin—nature or nurture? Clin Pharmacol Ther 2001; 70: 159–164.
- Magnusson MO, Dahl ML, Cederberg J, Karlsson MO, Sandstrom R. Pharmacodynamics of carbamazepine-mediated induction of CYP3A4, CYP1A2, and Pgp as assessed by probe substrates midazolam, caffeine, and digoxin. Clin Pharmacol Ther 2008; 84: 52–62.
- Margaglione M, Colaizzo D, D'Andrea G, Brancaccio V, Ciampa A, Grandone E, Di Minno G. Genetic modulation of oral anticoagulation with warfarin. Thromb Haemost 2000; 84: 775–778.
- Maurel P. The use of adult human hepatocytes in primary culture and other in vitro systems to investigate drug metabolism in man. Adv Drug Deliv Rev 1996; 22: 105–132.
- O'Mathuna B, Farre M, Rostami-Hodjegan A, Yang J, Cuyas E, Torrens M, Pardo R, Abanades S, Maluf S, Tucker GT, de la Torre R. The consequences of 3,4-methylenedioxymethamphetamine induced CYP2D6 inhibition in humans. J Clin Psychopharmacol 2008; 28: 523–529.
- Paine MF, Hart HL, Ludington SS, Haining RL, Rettie AE, Zeldin DC. The human intestinal cytochrome P450 “pie”. Drug Metab Dispos 2006; 34: 880–886.
- Paine MF, Khalighi M, Fisher JM, Shen DD, Kunze KL, Marsh CL, Perkins JD, Thummel KE. Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism. J Pharmacol Exp Ther 1997; 283: 1552–1562.
- Pang KS. Modeling of intestinal drug absorption: roles of transporters and metabolic enzymes (for the Gillette Review Series). Drug Metab Dispos 2003; 31: 1507–1519.
- Pichard L, Fabre I, Daujat M, Domergue J, Joyeux H, Maurel P. Effect of corticosteroids on the expression of cytochromes P450 and on cyclosporin A oxidase activity in primary cultures of human hepatocytes. Mol Pharmacol 1992; 41: 1047–1055.
- Pitlick WH, Levy RH, Tropin AS, Green JR. Pharmacokinetic model to describe self-induced decreases in steady-state concentrations of carbamazepine. J Pharm Sci 1976; 65: 462–463.
- Renwick AB, Watts PS, Edwards RJ, Barton PT, Guyonnet I, Price RJ, Tredger JM, Pelkonen O, Boobis AR, Lake BG. Differential maintenance of cytochrome P450 enzymes in cultured precision-cut human liver slices. Drug Metab Dispos 2000; 28: 1202–1209.
- Riley RJ, Grime K, Weaver R. Time-dependent CYP inhibition. Expert Opin Drug Metab Toxicol 2007; 3: 51–66.
- Ritter JK. Intestinal UGTs as potential modifiers of pharmacokinetics and biological responses to drugs and xenobiotics. Expert Opin Drug Metab Toxicol 2007; 3: 93–107.
- Rostami-Hodjegan A, Tucker GT. “In Silico” simulations to assess the “in vivo” consequences of “in vitro” metabolic drug—drug interactions. Drug Discovery Today: Technologies 2004; 1: 441–448.
- Rostami-Hodjegan A, Tucker GT. Simulation and prediction of in vivo drug metabolism in human populations from in vitro data. Nat Rev Drug Discov 2007; 6: 140–148.
- Rostami-Hodjegan A, Wolff K, Hay AW, Raistrick D, Calvert R, Tucker GT. Population pharmacokinetics of methadone in opiate users: characterization of time-dependent changes. Br J Clin Pharmacol 1999; 48: 43–52.
- Rowland M, Matin SB. Kinetics of drug—drug interactions. J Pharmacokinet Biopharm 1973; 1: 553–567.
- Russell TL, Berardi RR, Barnett JL, Dermentzoglou LC, Jarvenpaa KM, Schmaltz SP, Dressman JB. Upper gastrointestinal pH in seventy-nine healthy, elderly, North American men and women. Pharm Res 1993; 10: 187–196.
- Sconce EA, Khan TI, Wynne HA, Avery P, Monkhouse L, King BP, Wood P, Kesteven P, Daly AK, Kamali F. The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen. Blood 2005; 106: 2329–2333.
- Shou M, Hayashi M, Pan Y, Xu Y, Morrissey K, Xu L, Skiles GL. Modeling, prediction, and in vitro—in vivo correlation of CYP3A4 induction. Drug Metab Dispos 2008; 36: 2355–2370.
- Siguret V, Gouin I, Golmard JL, Geoffroy S, Andreux JP, Pautas E. [Cytochrome P450 2C9 polymorphisms (CYP2C9) and warfarin maintenance dose in elderly patients]. Rev Med Interne 2004; 25: 271–274.
- Tam D, Tirona RG, Pang KS. Segmental intestinal transporters and metabolic enzymes on intestinal drug absorption. Drug Metab Dispos 2003; 31: 373–383.
- Taube J, Halsall D, Baglin T. Influence of cytochrome P-450 CYP2C9 polymorphisms on warfarin sensitivity and risk of over-anticoagulation in patients on long-term treatment. Blood 2000; 96: 1816–1819.
- Tran JQ, Kovacs SJ, McIntosh TS, Davis HM, Martin DE. Morning spot and 24-hour urinary 6 beta-hydroxycortisol to cortisol ratios: intraindividual variability and correlation under basal conditions and conditions of CYP 3A4 induction. J Clin Pharmacol 1999; 39: 487–494.
- Venkatakrishnan K, Obach RS. In vitro—in vivo extrapolation of CYP2D6 inactivation by paroxetine: prediction of nonstationary pharmacokinetics and drug interaction magnitude. Drug Metab Dispos 2005; 33: 845–852.
- von Bahr C, Steiner E, Koike Y, Gabrielsson J. Time course of enzyme induction in humans: effect of pentobarbital on nortriptyline metabolism. Clin Pharmacol Ther 1998; 64: 18–26.
- Vrijens B, Goetghebeur E. The impact of compliance in pharmacokinetic studies. Stat Methods Med Res 1999; 8: 247–262.
- Warren JW Jr, Benmaman JD, Wannamaker BB, Levy RH. Kinetics of a carbamazepine—ethosuximide interaction. Clin Pharmacol Ther 1980; 28: 646–651.
- Watanabe T, Kusuhara H, Maeda K, Shitara Y, Sugiyama Y. Physiologically based pharmacokinetic modeling to predict transporter-mediated clearance and distribution of pravastatin in humans. J Pharmacol Exp Ther 2009; 328: 652–662.
- Watkins PB. Drug metabolism by cytochromes P450 in the liver and small bowel. Gastroenterol Clin North Am 1992; 21: 511–526.
- Yamashiro W, Maeda K, Hirouchi M, Adachi Y, Hu Z, Sugiyama Y. Involvement of transporters in the hepatic uptake and biliary excretion of valsartan, a selective antagonist of the angiotensin II AT1-receptor, in humans. Drug Metab Dispos 2006; 34: 1247–1254.
- Yang JS, Kjellsson M, Rostami-Hodjegan A, Tucker GT. The effects of dose staggering on metabolic drug—drug interactions. Eur J Pharm Sci 2003; 20: 223–232.
- Yang J, Jamei M, Yeo KR, Tucker GT, Rostami-Hodjegan A. Prediction of intestinal first-pass drug metabolism. Curr Drug Metab 2007; 8: 676–684.
- Yang J, Liao M, Shou M, Jamei M, Yeo KR, Tucker GT, Rostami-Hodjegan A. Cytochrome p450 turnover: regulation of synthesis and degradation, methods for determining rates, and implications for the prediction of drug interactions. Curr Drug Metab 2008; 9: 384–394.
- Yu LX, Amidon GL. Characterization of small intestinal transit time distribution in humans. Int J Pharm 1998; 171: 157–163.
- Zhang QY, Dunbar D, Ostrowska A, Zeisloft S, Yang J, Kaminsky LS. Characterization of human small intestinal cytochromes P-450. Drug Metab Dispos 1999; 27: 804–809.
- Zhao P, Ragueneau-Majlessi I, Zhang L, Strong JM, Reynolds KS, Lev RH, Thummel KE, Huang SM. Quantitative evaluation of pharmacokinetic inhibition of CYP3A substrates by ketoconazole—a simulation study. J Clin Pharmacol 2009; 49: 351–359.
