Are there differences in the catalytic activity per unit enzyme of recombinantly expressed and human liver microsomal cytochrome P450 2C9? A systematic investigation into inter-system extrapolation factors

Biopharmaceutics and Drug Disposition

Volumn 32, Issue 6, 2011, Pages 303-318

  Crewe, H K ^a,b   Barter, Z E ^a,b   Rowland Yeo, K ^b   Rostami Hodjegan, A ^a,b  

^a UNIVERSITY OF SHEFFIELD   (United Kingdom)

^b CERTARA UK LIMITED   (United Kingdom)

Author keywords

clearance prediction; CYP2C9; in vitro in vivo extrapolation (IVIVE); inter system extrapolation factor (ISEF); relative activity factors (RAF)

Indexed keywords

7 ETHOXYCOUMARIN; CYTOCHROME B5; CYTOCHROME P450 2C9; DICLOFENAC; RAF PROTEIN; RECOMBINANT CYTOCHROME P450 2C9; RECOMBINANT ENZYME; TOLBUTAMIDE; UNCLASSIFIED DRUG; WARFARIN;

ARTICLE; BODY SURFACE; CATALYSIS; GENETIC POLYMORPHISM; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN TISSUE; IN VITRO IN VIVO EXTRAPOLATION; INTER SYSTEM EXTRAPOLATION FACTOR; KIDNEY CLEARANCE; LIVER CLEARANCE; MAXIMUM PLASMA CONCENTRATION; METABOLIC RATE; METABOLISM; PARAMETER; PROTEIN EXPRESSION; RELATIVE ACTIVITY FACTOR; TECHNIQUE;

ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; ANTICOAGULANTS; ARYL HYDROCARBON HYDROXYLASES; CYTOCHROME P-450 ENZYME SYSTEM; CYTOCHROMES B5; DICLOFENAC; ENZYME ASSAYS; FORECASTING; HUMANS; HYPOGLYCEMIC AGENTS; LIVER; MICROSOMES, LIVER; MODELS, BIOLOGICAL; RECOMBINANT PROTEINS; TOLBUTAMIDE; WARFARIN;

EID: 80051906230     PISSN: 01422782     EISSN: 1099081X     Source Type: Journal    
DOI: 10.1002/bdd.760     Document Type: Article

References (56)

1. Crespi CL, Miller VP,. The use of heterologously expressed drug metabolizing enzymes-state of the art and prospects for the future. Pharmacol Ther 1999; 84: 121-131. (Pubitemid 29488547)
2. Zhang H, Davis CD, Sinz MW, et al,. Cytochrome P450 reaction-phenotyping: an industrial perspective. Expert Opin Drug Metab Toxicol 2007; 3: 667-687. (Pubitemid 351320636)
3. Harper TW, Brassil PJ,. Reaction phenotyping: current industry efforts to identify enzymes responsible for metabolizing drug candidates. AAPS J 2008; 10: 200-207.
4. Howgate EM, Rowland Yeo K, Proctor NJ, et al,. Prediction of in vivo drug clearance from in vitro data. I: impact of inter-individual variability. Xenobiotica 2006; 36: 473-497. (Pubitemid 43890728)
5. Rakhit A, Pantze MP, Fettner S, et al,. The effects of CYP3A4 inhibition on erlotinib pharmacokinetics: computer based simulation (SimCYP) predicts in vivo metabolic inhibition. Eur J Clin Pharmacol 2008; 64: 31-41.
6. Stringer RA, Strain-Damerell C, Nicklin P, et al,. Evaluation of recombinant cytochrome P450 enzymes as an in vitro system for metabolic clearance predictions. Drug Metab Dispos 2009; 37: 1025-1034.
7. Youdim KA, Zayed A, Dickins M, et al,. Application of CYP3A4 in vitro data to predict clinical drug-drug interactions; predictions of compounds as objects of interaction. Br J Clin Pharmacol 2008; 65: 680-692. (Pubitemid 351535079)
8. Carlile DJ, Hakooz N, Bayliss MK, et al,. Microsomal prediction of in vivo clearance of CYP2C9 substrates in humans. Br J Clin Pharmacol 1999; 47: 625-635. (Pubitemid 29257660)
9. Stringer R, Nicklin PL, Houston JB,. Reliability of human cryopreserved hepatocytes and liver microsomes as in vitro systems to predict metabolic clearance. Xenobiotica 2008; 38: 1313-1329.
10. 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. (Pubitemid 46745341)
11. Jamei M, Dickinson GL, Rostami-Hodjegan A,. A framework for assessing inter-individual 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 Pharmacokinet 2009; 24: 53-75.
12. Crespi CL,. Xenobiotic-metabolising human cells as tools for pharmacological and toxicological research. In Advances in Drug Research, Testa B, Meyer UA, (eds). Academic Press: New York, 1995; 179-235.
13. Venkatakrishnan K, von Moltke LL, Court MH, et al,. Comparison between cytochrome P450 (CYP) content and relative activity approaches to scaling from cDNA-expressed CYPs to human liver microsomes: ratios of accessory proteins as sources of discrepancies between the approaches. Drug Metab Dispos 2000; 28: 1493-1504.
14. Venkatakrishnan K, von Moltke LL, Greenblatt DJ,. 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 2001; 297: 326-337. (Pubitemid 32242593)
15. Nakajima M, Nakamura S, Tokudome S, et al,. Azelastine N-demethylation by cytochrome P-450 (CYP)3A4, CYP2D6, and CYP1A2 in human liver microsomes: evaluation of approach to predict the contribution of multiple CYPs. Drug Metab Dispos 1999; 27: 1381-1391.
16. Tang W, Wang RW, Lu AY,. Utility of recombinant cytochrome p450 enzymes: a drug metabolism perspective. Curr Drug Metab 2005; 6: 503-517. (Pubitemid 41300795)
17. Proctor NJ, Tucker GT, Rostami-Hodjegan A,. Predicting drug clearance from recombinantly expressed CYPs: intersystem extrapolation factors. Xenobiotica 2004; 34: 151-178. (Pubitemid 38299716)
18. Cubitt HE, Yeo KR, Howgate EM, et al,. Sources of interindividual variability in IVIVE of clearance: an investigation into the prediction of benzodiazepine clearance using a mechanistic population-based pharmacokinetic model. Xenobiotica 2011; (in press) Mar 24. [Epub ahead of print]
19. Rowland Yeo K, Rostami-Hodjegan A, Tucker GT,. Abundance of cytochromes P450 in human liver: a meta-analysis. Br J Clin Pharmacol 2004; 57: 687-688.
20. 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: 931-956. (Pubitemid 44299829)
21. Grime K, Riley RJ,. The impact of in vitro binding on in vitro-in vivo extrapolations, projections of metabolic clearance and clinical drug-drug interactions. Curr Drug Metab 2006; 7: 251-264.
22. Wilson ZE, Rostami-Hodjegan A, Burn JL, et al,. Inter-individual variability in levels of human microsomal protein and hepatocellularity per gram of liver. Br J Clin Pharmacol 2003; 56: 433-440. (Pubitemid 37188139)
23. Chauret N, Gauthier A, Nicoll-Griffith DA,. Effect of common organic solvents on in vitro cytochrome P450-mediated metabolic activities in human liver microsomes. Drug Metab Dispos 1998; 26: 1-4. (Pubitemid 28071316)
24. Brown HS, Griffin M, Houston JB,. Evaluation of cryopreserved human hepatocytes as an alternative in vitro system to microsomes for the prediction of metabolic clearance. Drug Metab Dispos 2007; 35: 293-301. (Pubitemid 46148743)
25. Obach RS,. Prediction of human clearance of twenty-nine drugs from hepatic microsomal intrinsic clearance data: An examination of in vitro half-life approach and nonspecific binding to microsomes. Drug Metab Dispos 1999; 27: 1350-1359.
26. Kilford PJ, Gertz M, Houston JB, et al,. Hepatocellular binding of drugs: correction for unbound fraction in hepatocyte incubations using microsomal binding or drug lipophilicity data. Drug Metab Dispos 2008; 36: 1194-1197. (Pubitemid 351929330)
27. Austin RP, Barton P, Cockroft SL, et al,. The influence of nonspecific microsomal binding on apparent intrinsic clearance, and its prediction from physicochemical properties. Drug Metab Dispos 2002; 30: 1497-1503. (Pubitemid 35397059)
28. Segal IH,. Enzyme kinetics: Behaviour and Analysis of Rapid Equilibrium and Steady State Enzyme Systems. John Wiley & Sons Inc.: New York, 1975.
29. Copeland RA,. Enzyme Kinetics. Wiley VCH Inc: New York, 1996.
30. Crespi Cl, Parkh S, Barter ZE, et al,. Twenty year, retrospective analysis of CYP activity levels in microsomes isolated from the human donor livers. Drug Metab Rev 2009; 41 (S3): 62-63.
31. Van LM, Hargreaves JA, Lennard MS, et al,. Inactivation of CYP2D6 by methylenedioxymethamphetamine in different recombinant expression systems. Eur J Pharm Sci 2007; 32: 8-16. (Pubitemid 47102186)
32. Wilkinson GR, Shand DG,. Commentary: a physiological approach to hepatic drug clearance. Clin Pharmacol Ther 1975; 18: 377-390.
33. Paine MF, Hart HL, Ludington SS, et al,. The human intestinal cytochrome P450 'pie'. Drug Metab Dispos 2006; 34: 880-886.
34. Barter ZE, Chowdry JE, Harlow JR, et al,. Covariation of human microsomal protein per gram of liver with age: absence of influence of operator and sample storage may justify interlaboratory data pooling. Drug Metab Dispos 2008; 36: 2405-2409.
35. Johnson TN, Tucker GT, Tanner MS, et al,. Changes in liver volume from birth to adulthood: a meta-analysis. Liver Transpl 2005; 11: 1481-1493. (Pubitemid 43072624)
36. Yang J, Tucker GT, Rostami-Hodjegan A,. Cytochrome P450 3A expression and activity in the human small intestine. Clin Pharmacol Ther 2004; 76: 391. (Pubitemid 39313131)
37. Yang J, Jamei M, Yeo KR, et al,. Prediction of intestinal first-pass drug metabolism. Curr Drug Metab 2007; 8: 676-684. (Pubitemid 47578116)
38. Mallikaarjun S, Bramer SL,. Effect of cilostazol on the pharmacokinetics and pharmacodynamics of warfarin. Clin Pharmacokinet 1999; 37 (Suppl 2): 79-86. (Pubitemid 30171190)
39. Madsen H, Enggaard TP, Hansen LL, et al,. Fluvoxamine inhibits the CYP2C9 catalyzed biotransformation of tolbutamide. Clin Pharmacol Ther 2001; 69: 41-47. (Pubitemid 32108670)
40. Leucuta A, Vlase L, Farcau D, et al,. No effect of short term ranitidine intake on diclofenac pharmacokinetics. Rom J Gastroenterol 2004; 13: 306-308.
41. Kumar V, Rock DA, Warren CJ, et al,. Enzyme source effects on CYP2C9 kinetics and inhibition. Drug Metab Dispos 2006; 34: 1903-1908. (Pubitemid 44771720)
42. Chen Y, Liu L, Nguyen K, et al,. Utility of inter-system extrapolation factors (ISEFs) in early reaction phenotyping and the quantitative extrapolation of human liver microsomal intrinsic clearance using recombinant cytochrome P450s. Drug Metab Dispos 2011; 39: 373-382.
43. Walsky RL, Obach RS,. Validated assays for human cytochrome P450 activities. Drug Metab Dispos 2004; 32: 647-660. (Pubitemid 38668158)
44. Wester MR, Lasker JM, Johnson EF, et al,. CYP2C19 participates in tolbutamide hydroxylation by human liver microsomes. Drug Metab Dispos 2000; 28: 354-359. (Pubitemid 30137062)
45. Tracy TS, Rosenbluth BW, Wrighton SA, et al,. Role of cytochrome P450 2C9 and an allelic variant in the 4'-hydroxylation of (R)- and (S)-flurbiprofen. Biochem Pharmacol 1995; 49: 1269-1275.
46. Hemeryck A, De Vriendt C, Belpaire FM,. Inhibition of CYP2C9 by selective serotonin reuptake inhibitors: in vitro studies with tolbutamide and (S)-warfarin using human liver microsomes. Eur J Clin Pharmacol 1999; 54: 947-951. (Pubitemid 29104416)
47. Tucker GT, Houston JB, Huang SM,. Optimizing drug development: strategies to assess drug metabolism/transporter interaction potential-towards a consensus. Br J Clin Pharmacol 2001; 52: 107-117. (Pubitemid 32862777)
48. Chang TK, Waxman DJ,. Catalytic assays for human cytochrome P450: an introduction. Methods Mol Biol 2006; 320: 73-83.
49. Williams PA, Cosme J, Ward A, et al,. Crystal structure of human cytochrome P450 2C9 with bound warfarin. Nature 2003; 424: 464-468. (Pubitemid 36917499)
50. 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; 34: 1966-1975. (Pubitemid 44837757)
51. Yamazaki H, Gillam EM, Dong MS, et al,. Reconstitution of recombinant cytochrome P450 2C10(2C9) and comparison with cytochrome P450 3A4 and other forms: effects of cytochrome P450-P450 and cytochrome P450-b5 interactions. Arch Biochem Biophys 1997; 342: 329-337. (Pubitemid 27251255)
52. Hummel MA, Tracy TS, Hutzler JM, et al,. Influence of fluorescent probe size and cytochrome b5 on drug-drug interactions in CYP2C9. J Biomol Screen 2006; 11: 303-309.
53. Locuson CW, Wienkers LC, Jones JP, et al,. CYP2C9 protein interactions with cytochrome b(5): effects on the coupling of catalysis. Drug Metab Dispos 2007; 35: 1174-1181. (Pubitemid 46956439)
54. McGinnity DF, Parker AJ, Soars M, et al,. Automated definition of the enzymology of drug oxidation by the major human drug metabolizing cytochrome P450s. Drug Metab Dispos 2000; 28: 1327-1334.
55. Mohutsky MA, Chien JY, Ring BJ, et al,. Predictions of the in vivo clearance of drugs from rate of loss using human liver microsomes for phase I and phase II biotransformations. Pharm Res 2006; 23: 654-662.
56. Youdim K, Dodia R,. Comparison between recombinant P450s and human liver microsomes in the determination of cytochrome P450 Michaelis-Menten constants. Xenobiotica 2010; 40: 235-244.