Skip to main content
SpringerLink
Log in

In Vitro/In Vivo Correlation for Drug–Drug Interactions

  • Reference work entry
Drug Discovery and Evaluation: Methods in Clinical Pharmacology

Abstract

Over the last 15 years, drug–drug interactions (DDIs) have become one of the emerging topics of the clinical drug development. For drugs with narrow therapeutic indices, the increase or decrease of plasma concentrations can lead to adverse effects or loss of efficacy, respectively. The increase of exposure caused by DDIs can be substantial (e.g., ketoconazole and midazolam with an interaction ratio of 16-fold for AUC is a well-known example) in particular with CYP3A4 (Fig. B.13-1 ). Indeed, health authorities released dedicated guidelines in the late 1990s, some of them recently updated (FDA Guidance for Industry 2006). In this context, simulations or predictions of DDI, bridging the gap between in vitro outcomes and clinical situation are challenging for the pharmaceutical industry, fueled by recent growth of knowledge in molecular biology, computer-based simulation/predictions, and a better understanding of the inhibition and induction mechanisms.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 549.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 549.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

REFERENCES AND FURTHER READING

  • Abramson FP (1986) Kinetic models of induction: I. Persistence of the inducing substance. J Pharm Sci 75(3):223–228

    Article  CAS  PubMed  Google Scholar 

  • Atkinson A, Kenny JR, Grime K (2005) Automated assessment of the time-dependent inhibition of human cytochrome P450 enzymes using liquid chromatography–tandem mass spectrometry analysis. Drug Metab Dispos 33:1637–1647

    Article  CAS  PubMed  Google Scholar 

  • Austin RD, Barton P, Cockroft SL, Wenlock MC, Riley RJ (2002) The influence of non-specific microsomal binding on apparent intrinsic clearance, and its prediction from physico-chemical properties. Drug Metab Dispos 30(12):1497–1503

    Article  CAS  PubMed  Google Scholar 

  • Bachmann KA (2006) Inhibition constants, inhibitor concentrations, and the predictions of inhibitory drug–drug interaction: pitfalls, progress and promise. Curr Drug Metab 7:1–14

    Article  CAS  PubMed  Google Scholar 

  • Back DJ, Orme ML’E (1989) Genetic factor influencing the metabolism of tolbutamide. Pharmacol Ther 44:147–155

    Article  CAS  PubMed  Google Scholar 

  • Beneth LZ, Hoener B (2002) Changes in plasma protein binding have little clinical relevance. Clin Pharm Ther 71(3):115–120

    Article  Google Scholar 

  • Bjornsson TD, Callaghan JT, Einolf HJ, Fischer V, Gan L, Grimm S, Kao J, King SP, Miwa G, Ni L (2003) The conduct of in vitro and in vivo drug–drug interaction studies: a pharmaceutical research and manufacturers of America (PhRMA) perspective. Drug Metab Dispos 31:815–832

    Article  CAS  PubMed  Google Scholar 

  • Blanchard N, Richert L, Coassolo P, Lave T (2004) Qualitative and quantitative assessment of drug–drug interaction potential in man, based on K i , IC50, and inhibitor concentrations. Curr Drug Metab 5:147–156

    Article  CAS  PubMed  Google Scholar 

  • Brown HS, Ito K, Galetin A, Houston JB (2005) Prediction of in vivo drug–drug interactions from in vitro data: impact of incorporating parallel pathways of drug elimination and inhibitor absorption rate constant. Br J Clin Pharmacol 60:508–518

    Article  CAS  PubMed  Google Scholar 

  • Brown HS, Galetin A, Hallifax D, Houston JB (2006) Prediction of in vivo drug–drug interactions from in vitro data: factors affecting prototypic drug–drug interactions involving CYP2C9, CYP2D6 and CYP3A4. Clin Pharmacokinet 45:1035–1050

    Article  CAS  PubMed  Google Scholar 

  • Correia MA, Liao M (2007) Cellular proteolytic systems in P450 degradation: evolutionary conservation from Saccharomyces cerevisiae to mammalian liver. Expert Opin Drug Metab Toxicol 3(1):33–49

    Article  CAS  PubMed  Google Scholar 

  • Crespi CL (1995) Xenobiotic-metabolizing human cells as tools for pharmacological and toxicological research. Adv Drug Res 26:179–235

    Article  CAS  Google Scholar 

  • De Buck SS, Mackie CE (2007) Physiologically based approaches towards the prediction of pharmacokinetics: in vitro–in vivo extrapolation. Expert Opin Drug Metab Toxicol 3(6):865–878

    Article  PubMed  Google Scholar 

  • Di L, Kerns EH, Li SQ, Carter GT (2007) Comparison of cytochrome P450 inhibition assays for drug discovery using human liver microsomes with LC-MS, rhCYP450 isozymes with fluorescence, and double cocktail with LC-MS. Int J Pharm 335(1–2):1–11

    Article  CAS  PubMed  Google Scholar 

  • Dong JQ, Gibbs BC, Emery M (2008) Applications of computer-aided pharmacokinetic and pharmacodynamic methods form drug discovery to registration. Curr Comput Aided Drug Des 4:54–66

    Article  CAS  Google Scholar 

  • Edginton AN, Theil FP, Schmitt W, Wilmann S (2008) Whole body physiologically-based pharmacokinetic models: their use in clinical development. Expert Opin Drug Metab Toxicol 4(9):1143–1152

    Article  CAS  PubMed  Google Scholar 

  • Egnell A-C, Eriksson C, Albertson N, Houston JB, Boyer S (2003) Generation and evaluation of CYP2C9 heteroactivation pharmacophore. J Pharmacol Exp Ther 307:878–887

    Article  CAS  PubMed  Google Scholar 

  • Einolf HJ (2007) Comparison of different approaches to predict metabolic drug–drug interactions. Xenobiotica 37(10):1257–1294

    Article  CAS  PubMed  Google Scholar 

  • Elshourbagy NA, Barwick JL, Guzelian PS (1981) Induction of cytochrome P-450 by pregnenolone-16 alpha-carbonitrile in primary monolayer cultures of adult rat hepatocytes and in a cell-free translation system. J Biol Chem 256(12):6060–6068

    CAS  PubMed  Google Scholar 

  • Emoto C, Iwasaki K (2007) Approach to predict the contribution of cytochrome P450 enzymes to drug metabolism in the early drug-discovery stage: the effect of the expression of cytochrome b5 with recombinant P450 enzymes. Xenobiotica 37:986–999

    Article  CAS  PubMed  Google Scholar 

  • Emoto C, Murase S, Iwasaki K (2006) Approach to the prediction of the contribution of major cytochrome P450 enzymes to drug metabolism in the early drug-discovery stage. Xenobiotica 36:671–683

    Article  CAS  PubMed  Google Scholar 

  • Espié P, Tytgat D, Sargentini-Maier ML, Poggesi I, Watelet JB (2009) Physiologically based pharmacokinetics (PBPK). Drug Metab Rev 41(3):391–407

    Article  PubMed  CAS  Google Scholar 

  • Fahmi OA, Maurer TS, Kish M, Cardenas E, Boldt S, Nettleton D (2008) A combined model for predicting CYP3A4 clinical net drug–drug interaction based on CYP3A4 inhibition, inactivation, and induction determined in vitro. Drug Metab Dispos 36:1698–1708

    Article  CAS  PubMed  Google Scholar 

  • Fahmi OA, Hurst S, Plowchalk D, Cook J, Guo F, Youdim K, Dickins M, Phipps A, Darekar A, Hyland R, Obach RS (2009) 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 37:1658–1666

    Article  CAS  PubMed  Google Scholar 

  • FDA Guidance for Industry (2006) Drug interaction studies: study design, data analysis, and implications for dosing and labeling http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM072101.pdf

  • Foti RS, Wahlstrom JL (2008) CYP2C19 inhibition: the impact of substrate probe selection on in vitro inhibition profiles. Drug Metab Dispos 36:523–528

    Article  CAS  PubMed  Google Scholar 

  • Fowler S, Zhang H (2008) In vitro evaluation of reversible and irreversible Cytochrome P450 inhibition: current status on methodologies and their utility for predicting drug–drug. AAPS J 10(2):410–424

    Article  CAS  PubMed  Google Scholar 

  • Galetin A (2007) Intestinal first-pass metabolism: bridging the gap between in vitro and in vivo. Curr Drug Metab 8(7):643–654

    Article  CAS  PubMed  Google Scholar 

  • Galetin A, Clarke SE, Houston JB (2003) Multisite kinetic analysis of interactions between prototypical CYP3A4subgroup substrates, midazolam, testosterone, and nifedipine. Drug Metab Dispos 31:1108–1116

    Article  CAS  PubMed  Google Scholar 

  • Galetin A, Ito K, Hallifax D, Houston JB (2005) CYP3A4 substrate selection and substitution in the prediction of potential drug–drug interactions. J Pharmacol Exp Ther 314:118–190

    Article  CAS  Google Scholar 

  • Galetin A, Burt H, Gibbons L, Houston JB (2006) Prediction of time-dependent CYP3A4 drug–drug interactions: impact of enzyme degradation, parallel elimination pathways, and intestinal inhibition. Drug Metab Dispos 34(1):166–175

    Article  CAS  PubMed  Google Scholar 

  • Galetin A, Hinton LK, Burt H, Obach RS, Houston JB (2007) Maximal inhibition of intestinal first-pass metabolism as a pragmatic indicator of intestinal contribution to the drug–drug interactions for CYP3A4 cleared drugs. Curr Drug Metab 8(7):685–693

    Article  CAS  PubMed  Google Scholar 

  • Galetin A, Gertz M, Houston JB (2008) Potential role of intestinal first-pass metabolism in the prediction of drug–drug interactions. Expert Opin Drug Metab Toxicol 4(7):909–922

    Article  CAS  PubMed  Google Scholar 

  • Ghanbari F, Rowland-Yeo K, Bloor JC, Clarke SE, Lennard MS, Tucker GT, Rostarni-Hodjegan A (2006) 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 7:315–334

    Article  CAS  PubMed  Google Scholar 

  • Gibbs MA, Kunze KL, Howald WN, Thummel KE (1999) Effect of inhibitor depletion on inhibitory potency: tight binding inhibition of CYP3A by clotrimazole. Drug Metab Dispos 27:596–599

    CAS  PubMed  Google Scholar 

  • Gibbs JP, Hyland R, Youdim K (2006) Minimizing polymorphic metabolism in drug discovery: evaluation of the utility of in vitro methods for predicting pharmacokinetic consequences associated with CYP2D6 metabolism. Drug Metab Dispos 34(9):1516–1522

    Article  CAS  PubMed  Google Scholar 

  • Grime KH, Bird J, Ferguson D, Riley RJ (2009) Mechanism-based inhibition of cytochrome P450 enzymes: an evaluation of early decision making in vitro approaches and drug–drug interaction prediction methods. Eur J Pharm Sci 36:175–191

    Article  CAS  PubMed  Google Scholar 

  • Guillouzo A, Beaune P, Gascoin MN, Begue JM, Campion JP, Guengerich FP, Guguen-Guillouzo C (1985) Maintenance of cytochrome P-450 in cultured adult human hepatocytes. Biochem Pharmacol 34(16):2991–2995

    Article  CAS  PubMed  Google Scholar 

  • Hallifax D, Houston JB (2006) Binding of drugs to hepatic microsomes: comment and assessment of prediction methodology with recommendation for improvement. Drug Metab Dispos 34(4): 724–726

    Article  CAS  PubMed  Google Scholar 

  • Henshall J, Galetin A, Harrison A, Houston JB (2008) Comparative analysis of CYP3A heteroactivation by steroid hormones and flavonoids in different in vitro systems and potential in vivo implications. Drug Metab Dispos 36:1332–1340

    Article  CAS  PubMed  Google Scholar 

  • Houston JB, Galetin A (2005) Modelling atypical CYP3A4 kinetics: principles and pragmatism. Arch Biochem Biophys 433:351–360

    Article  CAS  PubMed  Google Scholar 

  • Hutzler JM, Wienkers LC, Wahlstrom JL, Carlson TJ, Tracy TS (2003) Activation of cytochrome P450 2C9-mediated metabolism: mechanistic evidence in support of kinetic observations. Arch Biochem Biophys 410:16–24

    Article  PubMed  Google Scholar 

  • Ito K, Iwatsubo T, Kanamitsu S, Ueda K, Suzuki H, Sugiyama Y (1998) Prediction of pharmacokinetic alterations caused by drug–drug interactions: metabolic interaction in the liver. Pharmacol Rev 50(3):387–412

    CAS  PubMed  Google Scholar 

  • Ito K, Chiba K, Horikawa M, Ishigami M, Mizuno N, Aoki J, Gotoh Y, Iwatsubo T, Kanamitsu S, Kato M, Kawahara I, Niinuma K, Nishino A, Sato N, Tsukamoto Y, Ueda K, Itoh T, Sugiyama Y (2002) Which concentration of the inhibitor should be used to predict in vivo drug interactions from in vitro data? AAPS Pharm Sci 4:article 25

    Google Scholar 

  • Ito K, Brown HS, Houston JB (2004) Database analysis for the prediction of in vivo drug–drug interactions from in vitro data. Br J Clin Pharmacol 57(4):473–486

    Article  CAS  PubMed  Google Scholar 

  • Ito K, Hallifax D, Obach RS, Houston JB (2005) Impact of parallel pathways of drug elimination and multiple CYP involvement on drug–drug interactions: CYP2D6 paradigm. Drug Metab Dispos 33:837–844

    Article  CAS  PubMed  Google Scholar 

  • Jamei M, Marciniack S, Feng K, Barnett A, Tucker G, Rostani-Hodjegan A (2009) The Simcyp population-based ADME simulator. Expert Opin Metab Drug Toxicol 5(2):211–223

    Article  CAS  Google Scholar 

  • Jones HM, Houston JB (2004) Substrate depletion approach for determining in vitro metabolic clearance: time dependencies in hepatocyte and microsomal incubations. Drug Metab Dispos 32:973–982

    Article  CAS  PubMed  Google Scholar 

  • Kalvass JC, Tess DA, Giragossian C, Linhares MC, Maurer TS (2001) Influence of microsomal concentration on apparent intrinsic clearance: implications for scaling in vitro data. Drug Metab Dispos 29:1332–1336

    CAS  PubMed  Google Scholar 

  • Kanamitsu S, Ito K, Sugiyama Y (2000) Quantitative prediction of in vivo drug–drug interactions from in vitro data based on physiological pharmacokinetics: use of maximum unbound concentration of inhibitor at the inlet to the liver. Pharm Res 17:336–343

    Article  CAS  PubMed  Google Scholar 

  • Kitz R, Wilson IB (1962) Esters of methanesulfonic acid as irreversible inhibitors of acetylcholinesterase. J Biol Chem 237:3245–3249

    CAS  PubMed  Google Scholar 

  • Lake BG, Charzat C, Tredger JM, Renwick AB, Beamand JA, Price RJ (1996) Induction of cytochrome P450 isoenzymes in cultured precision-cut rat and human liver slices. Xenobiotica 26(3):297–306

    Article  CAS  PubMed  Google Scholar 

  • Lasker JM (2002) Expression and induction of CYP2C P450 enzymes in primary cultures of human hepatocytes. J Pharmacol Exp Ther 302(2):475–482

    Article  PubMed  CAS  Google Scholar 

  • LeCluyse EL (2001) Human hepatocyte culture systems for the in vitro evaluation of cytochrome P450 expression and regulation. Eur J Pharm Sci 13(4):343

    Article  CAS  PubMed  Google Scholar 

  • Levy RH (1986) In: Rowland M, Tucker GT (eds) Pharmacokinetics: theory and methodology. Pergamon Press, Oxford, pp 115–130

    Google Scholar 

  • Li AP, Maurel P, GomezLechon MJ, Cheng LC, JurimaRomet M (1997) Preclinical evaluation of drug–drug interaction potential: present status of the application of primary human hepatocytes in the evaluation of cytochrome P450 induction. Chem Biol Interact 107(1–2):5–16

    Article  CAS  PubMed  Google Scholar 

  • Lin JH, Chiba M, Baillie TA (1999) Is the role of the small intestine in first-pass metabolism overemphasized? Pharmacol Rev 51:135–158

    CAS  PubMed  Google Scholar 

  • Margolis JM, Obach RS (2003) Impact of nonspecific binding to microsomes and phospholipids on the inhibition of cytochrome P4502D6: implications for relating in vitro inhibition data to in vivo drug interactions. Drug Metab Dispos 31:606–611

    Article  CAS  PubMed  Google Scholar 

  • McGinnity DF, Waters NJ, Tucker J, Riley RJ (2008) Integrated in vitro analysis for the in vivo prediction of cytochrome P450-mediated drug–drug interactions. Drug Metab Dispos 36:1126–1134

    Article  CAS  PubMed  Google Scholar 

  • Nakajima M, Tane K, Nakamura S, Shimada N, Yamazaki H, Yokoi T (2002) Evaluation of approach to predict the contribution of multiple cytochrome P450s in drug metabolism using relative activity factor: effects of the differences in expression levels of NADPH–cytochrome P450 reductase and cytochrome b(5) in the expression system and the differences in the marker activities. J Pharm Sci 91:952–963

    Article  CAS  PubMed  Google Scholar 

  • Newman SL, Barwick JL, Elshourbagy NA, Guzelian PS (1982) Measurement of the metabolism of cytochrome P-450 in cultured hepatocytes by a quantitative and specific immunochemical method. Biochem J 204(1):281–290

    CAS  PubMed  Google Scholar 

  • Obach RS (1996) The importance of nonspecific binding in in vitro matrices, its impact on enzyme kinetic studies of drug metabolism reactions and implications for in vitro–in vivo correlations. Drug Metab Dispos 24:1047–1049

    CAS  PubMed  Google Scholar 

  • Obach RS (1997) Nonspecific binding to microsomes. Drug Metab Dispos 25:1359–1369

    CAS  PubMed  Google Scholar 

  • Obach RS, Baxter JG, Liston TE, Silber BM, Jones BC, MacIntyre F, Rance DJ, Wastall P (1997) The prediction of human pharmacokinetic parameters from preclinical and in vitro metabolism data. J Pharmacol Exp Ther 283:46–58

    CAS  PubMed  Google Scholar 

  • Obach RS, Walsky RL, Venkatakrishnan K, Houston JB, Tremaine LM (2005) In vitro cytochrome P450 inhibition data and the prediction of drug–drug interactions: qualitative relationships, quantitative predictions, and the rank-order approach. Clin Pharmacol Ther 78:582–592

    Article  CAS  PubMed  Google Scholar 

  • Obach RS, Walsky RL, Venkatakrishnan K, Gaman EA, Houston JB, Tremaine LM (2006) The utility of in vitro cytochrome P450 inhibition data in the prediction of drug–drug interactions. J Pharmacol Exp Ther 316(1):336–348

    Article  CAS  PubMed  Google Scholar 

  • Obach RS, Walsky RL, Venkatakrishnan K (2007) Mechanism-based inactivation of human cytochrome p450 enzymes and the prediction of drug–drug interactions. Drug Metab Dispos 35:246–255

    Article  CAS  PubMed  Google Scholar 

  • Ohno Y, Hisaka A, Suzuki H (2007) General framework for the quantitative prediction of CYP3A4-mediated oral drug interactions based on the AUC increase by coadministration of standard drugs. Clin Pharmacokinet 46:681–696

    Article  CAS  PubMed  Google Scholar 

  • Ohno Y, Hisaka A, Ueno M, Suzuki H (2008) General framework for the prediction of oral drug interactions caused by CYP3A4 induction from in vivo information. Clin Pharmacokinet 47:669–680

    Article  CAS  PubMed  Google Scholar 

  • Paine AJ (1990) The maintenance of cytochrome P-450 in rat hepatocyte culture: some applications of liver cell cultures to the study of drug metabolism, toxicity and the induction of the P-450 system. Chem Biol Interact 74(1–2):1–31

    Article  CAS  PubMed  Google Scholar 

  • Paine MF, Khalighi M, Fisher JM (1997) Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism. J Pharmacol Exp Ther 283:1552–1556

    CAS  PubMed  Google Scholar 

  • Paine MF, Hart HL, Ludington SS (2006) The human intestinal cytochrome P450 "pie". Drug Metab Dispos 34:880–886

    Article  CAS  PubMed  Google Scholar 

  • Proctor NJ, Tucker GT, Rostami-Hodjegan A (2004) Predicting drug clearance from recombinantly expressed CYPs: intersystem extrapolation factors. Xenobiotica 34:151–178

    Article  CAS  PubMed  Google Scholar 

  • Renwick AB, Watts PS, Edwards RJ, Barton PT, Guyonnet I, Price RJ, Tredger JM, Pelkonen O, Boobis AR, Lake BG (2000) Differential maintenance of cytochrome P450 enzymes in cultured precision-cut human liver slices. Drug Metab Dispos 28(10):1202–1209

    CAS  PubMed  Google Scholar 

  • Rodrigues AD (1999) Integrated cytochrome P450 reaction phenotyping: attempting to bridge the gap between cDNA-expressed cytochromes P450 and native human liver microsomes. Biochem Pharmacol 57(5):465–480

    Article  CAS  PubMed  Google Scholar 

  • Rodrigues AD (ed) (2002) Drug–drug interactions. Drugs and the pharmaceutical sciences, vol 116. Marcel Dekker, New York

    Google Scholar 

  • Rostami-Hodjegan A, Tucker G (2004) ‘In silico’ simulations to assess the ‘in vivo’ consequences of ‘in vitro’ metabolic drug–drug interactions. Drug Discov Today 1(4):441–448

    CAS  Google Scholar 

  • Rostami-Hodjegan A, Tucker G (2007) Simulation and prediction of in vivo drug metabolism in human population from in vitro data. Nat Rev Drug Discov 6:140–148

    Article  CAS  PubMed  Google Scholar 

  • Rowland M, Matin SB (1973) Kinetics of drug–drug interactions. J Pharmacokinet Biopharm 1:553–567

    Article  CAS  Google Scholar 

  • Rowland Yeo K, Rostami-Hodjegan A, Tucker GT (2004) Abundance of cytochromes P450 in human liver: a meta analysis. Proceedings of the British Pharmacological Society, vol 1, 225P

    Google Scholar 

  • Schmitt W, Wilmann S (2004) Physiology-based pharmacokinetic model: ready to be used. Drug Discov Today Technol 1(4):449–456

    Article  CAS  Google Scholar 

  • Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP (1994) 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 270:414–423

    CAS  PubMed  Google Scholar 

  • Shitara Y, Hirano M, Sato H (2004) Gemfibrozil and it glucuronide inhibit the organic anion transporting polypeptide 2 (OATP1B1)-mediated hepatic uptake and CYP2C8-mediated metabolism of cerivastatin: analysis of the mechanism of the clinically relevant drug–drug interaction between cerivatstain and gemfobrozil. J Pharmacol Exp Ther 311:228–236

    Google Scholar 

  • Shou M, Hayashi M, Pan Y, Yang Y, Morrissey K, Xu L, Skiles GL (2008) Modeling, prediction, and in vitro in vivo correlation of CYP3A4 induction. Drug Metab Dispos 36:2355–2370

    Article  CAS  PubMed  Google Scholar 

  • Silverman RB (1988) Mechanism-based enzyme inactivation in chemistry and enzymology, vol 1. CRC Press, Boca Raton, pp 3–30

    Google Scholar 

  • Silverman RB (1995) Mechanism-based enzyme inactivators. Methods Enzymol 249:240–283

    Article  CAS  PubMed  Google Scholar 

  • Soars MG, Burchell B, Riley RJ (2002) In vitro analysis of human drug glucuronidation and prediction of in vivo metabolic clearance. J Pharmacol Exp Ther 301:382–390

    Article  CAS  PubMed  Google Scholar 

  • Stormer E, Von Moltke LL, GreenBlatt DJ (2000) Scaling drug biotransformation data from cDNA-expressed cytochrome P-450 to human liver: a comparison of relative activity factors and human liver abundance in studies of mirtazapine metabolism. J Pharmacol Exp Ther 293:793–801

    Google Scholar 

  • Toide K, Terauchi Y, Fujii T, Yamazaki H, Kamataki T (2004) Uridine diphosphate sugar-selective conjugation of an aldose reductase inhibitor (AS-3201) by UDP-glucuronosyltransferase 2B subfamily in human liver microsomes. Biochem Pharmacol 67:1269–1278

    Article  CAS  PubMed  Google Scholar 

  • Tran TH, Von Moltke LL, Venkatakrishnan K, Granda BW, Gibbs MA, Obach RS, Harmatz JS, Greenblatt DJ (2002) Microsomal protein concentration modifies the apparent inhibitory potency of CYP3A inhibitors. Drug Metab Dispos 30:1441–1445

    Article  CAS  PubMed  Google Scholar 

  • Tucker GT (1992) The rational selection of drug interaction studies: implications of recent advances in drug metabolism. Int J Clin Pharmacol Ther Toxicol 30:550–553

    CAS  PubMed  Google Scholar 

  • Tucker GT, Houston JB, Huang S-M (2001) Optimizing drug development: strategies to assess drug metabolism/transporter interaction potential: toward a consensus. Clin Pharmacol Ther 70:103–114

    Article  CAS  PubMed  Google Scholar 

  • Uchaipichat V, Mackenzie PI, Guo X-H, Gardner-Stephen D, Galetin A, Houston JB, Miners JO (2004) Human UDP-glucuronosyltransferases: isoform selectivity and kinetics of 4-methylumbelliferone and 1-naphthol glucuronidation, effects of organic solvents and inhibition by diclofenac and probenecid. Drug Metab Dispos 32:413–423

    Article  CAS  PubMed  Google Scholar 

  • Venkatakrishnan K, Obach RS (2005) In vitro–in vivo extrapolation of CYP2D6 inactivation by paroxetine: prediction of non stationary pharmacokinetics of drug interaction magnitude. Drug Metab Dispos 33(6):845–852

    Article  CAS  PubMed  Google Scholar 

  • Venkatakrishnan K, Obach RS (2007) Drug–drug interactions v/a mechanism-based cytochrome P450 inactivation: points to consider for risk assessment from in vitro data and clinical pharmacologic evaluation. Curr Drug Metab 8:449–462

    Article  CAS  PubMed  Google Scholar 

  • Venkatakrishnan K, von Moltke LL, Obach RS, Greenblatt DJ (2000) Microsomal binding of amitriptyline: effect on estimation of enzyme kinetic parameters in vitro. J Pharmacol Exp Ther 293:343–350

    CAS  PubMed  Google Scholar 

  • Venkatakrishnan K, von Moltke LL, Greenblatt DJ (2001) Application of the relative activity factor approach in scaling from heterologously expressed cytochromes P450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther 297:326–337

    CAS  PubMed  Google Scholar 

  • Walsky RL, Obach RS (2004) Validated assays for human cytochrome P450 activities. Drug Metab Dispos 32(6):647–660

    Article  CAS  PubMed  Google Scholar 

  • Walsky RL, Gaman EA, Obach RS (2005) Examination of 209 drugs for inhibition of cytochrome P4502C8. J Clin Pharmacol 45(1):68–78

    Article  CAS  PubMed  Google Scholar 

  • Walsky RL, Astuccio AV, Obach RS (2006) Evaluation of 227 drugs for in vitro inhibition of cytochrome P450 2B6. J Clin Pharmacol 46(12):1426–1438

    Article  CAS  PubMed  Google Scholar 

  • Wang YH, Jones DR, Hall SD (2004) Prediction of cytochrome P450 3A inhibition by verapamil enantiomers and their metabolites. Drug Metab Dispos 32:259–266

    Article  CAS  PubMed  Google Scholar 

  • Wright MC, Paine AJ (1992) Evidence that the loss of rat liver cytochrome P450 in vitro is not solely associated with the use of collagenase, the loss of cell–cell contacts and/or the absence of an extracellular matrix. Biochem Pharmacol 43(2):237–243

    Article  CAS  PubMed  Google Scholar 

  • Yang J, Tucker GT, Rostami-Hodjegan A (2004) Cytochrome P450 3A expression and activity in the human small intestine. Clin Pharmacol Ther 76:391

    Article  CAS  PubMed  Google Scholar 

  • Yang J, Jamei M, Rowland YK, Rostami-Hodjegan A, Tucker GT (2005) Kinetic values for mechanism-based inhibition: assessment of bias introduced by the conventional experimental protocol. Eur J Pharm Sci 26:334–340

    Article  CAS  PubMed  Google Scholar 

  • Yang J, Jamei M, Roland YK, Ticker GT, Rostami-Hodjegan A (2007a) Prediction of intestinal first-pass drug metabolism. Curr Drug Metab 8:676–684

    Article  CAS  PubMed  Google Scholar 

  • Yang J, Jamei M, Rowland Yeo K, Tucker GT, Rostami-Hodjegan A (2007b) Theoretical assessment of a new experimental protocol for determining kinetic values describing mechanism (time)-based enzyme inhibition. Eur J Pharm Sci 26:334–340

    Article  CAS  Google Scholar 

  • Yang J, Liao M, Shou M, Jamei M, Rowland Yeo K, Tucker GT, Rostami-Hodjegan A (2008) Cytochrome P450 turnover: regulation of synthesis and degradation, methods for determining rates, and implications for the prediction of drug interactions. Curr Drug Metab 9:384–393

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Davis CD, Sinz MW, Rodrigues D (2007) Cytochrome P450 reaction-phenotyping: an industrial perspective. Exp Opin Drug Metab Toxicol 3(5):667–687

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. MPK Clinique Global Metabolism and Pharmacokinetic Department, Sanofi-Aventis Research and Development, 371, Rue du Professeur Joseph Blayac, 34184, Montpellier Cedex 04, France

    Xavier Boulenc

  2. R&D Metabolism and PK Germany, Sanofi-Aventis Deutschland GmbH, Industriepark Hoechst Building G876, 65926, Frankfurt am Main, Germany

    Wolfgang Schmider

  3. Aureus Pharma, 174 Quai de Jemmapes, 75010, Paris, France

    Olivier Barberan

Authors
  1. Xavier Boulenc
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wolfgang Schmider
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Olivier Barberan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xavier Boulenc .

Editor information

Editors and Affiliations

  1. Bohl Str. 28, 73430, Aalen, Germany

    Hans Gerhard Vogel

  2. Sanofi Aventis Deutschland GmbH, Industriepark Hoechst, Building G877, R&D Metabolism and PK Germany, 65926, Frankfurt am Main, Germany

    Jochen Maas

  3. Merz Pharmaceuticals GmbH, Eckenheimer Landstraβe 100, 60318, Frankfurt am Main, Germany

    Alexander Gebauer

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer-Verlag Berlin Heidelberg

About this entry

Cite this entry

Boulenc, X., Schmider, W., Barberan, O. (2011). In Vitro/In Vivo Correlation for Drug–Drug Interactions. In: Vogel, H.G., Maas, J., Gebauer, A. (eds) Drug Discovery and Evaluation: Methods in Clinical Pharmacology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-89891-7_14

Download citation

Publish with us

Policies and ethics

Search

Navigation