A comparison of relative abundance, activity factor and inhibitory monoclonal antibody approaches in the characterization of human CYP enzymology

British Journal of Clinical Pharmacology

Volumn 55, Issue 2, 2003, Pages 175-181

  Soars, Matthew G ^a   Gelboin, Harry V ^b   Krausz, Kristopher W ^b   Riley, Robert J ^a  

^a ASTRAZENECA   (United Kingdom)

^b NATIONAL CANCER INSTITUTE   (United States)

Author keywords

HLM monoclonal antibody; Intrinsic clearance; Reaction phenotyping; Recombinant CYP

Indexed keywords

BUFURALOL; CYTOCHROME P450; CYTOCHROME P450 1A2; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; CYTOCHROME P450C19; DEXTROMETHORPHAN; DICLOFENAC; DILTIAZEM; ETHOXYRESORUFIN; ISOPROTEIN; LIVER ENZYME; MEPHENYTOIN; METOPROLOL; MONOCLONAL ANTIBODY; NAPROXEN; OMEPRAZOLE; PHENACETIN; PROPRANOLOL; RECOMBINANT ENZYME; TESTOSTERONE; TOLBUTAMIDE; UNCLASSIFIED DRUG; VERAPAMIL;

AEROBIC METABOLISM; ANALYTIC METHOD; ARTICLE; CATALYSIS; CLEARANCE; CONTROLLED STUDY; DRUG METABOLISM; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME METABOLISM; ENZYMOLOGY; HUMAN; HUMAN TISSUE; INTERMETHOD COMPARISON; LIVER METABOLISM; LIVER MICROSOME; MOLECULAR PROBE; PHENOTYPE; PRIORITY JOURNAL; PROTEIN FAMILY; RELATIVE ACTIVITY FACTOR; TECHNIQUE;

ANTIBODIES, MONOCLONAL; CYTOCHROME P-450 ENZYME SYSTEM; DRUG DESIGN; HUMANS; PHENOTYPE;

EID: 0344255758     PISSN: 03065251     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1365-2125.2003.01721.x     Document Type: Article

References (29)

1. Bertz RJ, Granneman GR. Use of in vitro and in vivo data to estimate the likelihood of metabolic pharmacokinetic interactions. Clin Pharmacokinet 1997; 32: 210-258.
2. Riley RJ. The potential pharmacological and toxicological impact of P450 screening. Curr Opin Drug Discovery Dev 2001; 4: 45-54.
3. McGinnity DF, Griffin SJ, Moody GC et al. Rapid characterization of the major drug-metabolizing human hepatic cytochrome P-450 enzymes expressed in Escherichia coli. Drug Metab Dispos 1999; 27: 1017-1023.
4. Eddershaw PJ, Dickins M. Advances in in vitro drug metabolism screening. Pharm Sci Technol Today 1999; 2: 13-19.
5. McGinnity DF, Parker AJ, Soars M, Riley RJ. Automated definition of the enzymology of drug oxidation by the major human drug metabolizing cytochrome P450s. Drug Metab Dispos 2000; 28: 1327-1334.
6. Crespi CL. Xenobiotic-metabolizing human cells as tools for pharmacological and toxicological research. Adv Drug Res 1995; 26: 179-235.
7. Kobayashi K, Chiba K, Yagi T et al. Identification of cytochrome P450 isoforms involved in citalopram N-demethylation by human liver microsomes. J Pharmacol Exp Ther 1997; 280: 927-933.
8. Venkatakrishnan K, Von Moltke LL, Greenblatt DJ. Relative quantities of catalytically active CYP2C9 and 2C19 in human liver microsomes: application of the relative activity factor approach. J Pharm Sci 1998; 87: 845-853.
9. Von Moltke LL, Greenblatt DJ, Grassi JM et al. Multiple human cytochromes contribute to biotransformation of dextromethorphan in vitro: role of CYP2C9, CYP2C19, CYP2D6, and CYP3A. J Pham Pharmacol 1998; 50: 997-1004.
10. Nakajima M, Nakamura S, Tokudome S, Shimada N, Yamazaki H, Yokoi T. 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.
11. Yang TJ, Sai T, Krausz KW, Gonzalez FJ, Gelboin HV. Inhibitory monoclonal antibodies to human cytochrome P450 1A2: analysis of phenacetin O-de-ethylation in human liver. Pharmacogenetics 1997; 8: 375-382.
12. Krausz KW, Goldfarb I, Buters JTM, Yang TJ, Gonzalez FJ, Gelboin HV. Monoclonal antibodies specific and inhibitory to human cytochromes P450 2C8, 2C9, and 2C19. Drug Metab Dispos 2001; 29: 1410-1423.
13. Gelboin HV, Krausz KW, Sbou M, Gonzalez FJ, Yang TJ. A monoclonal antibody inhibitory to human P450 2D6: a paradigm for use in combinatorial determination of individual P450 role in specific drug tissue metabolism. Pharmacogenetics 1997; 7: 469-477.
14. Gelboin HV, Krausz KW, Goldfarb I et al. Inhibitory and non-inhibitory monoclonal antibodies to human cytochrome P450 3A3/4. Biochem Pharmacol 1995; 50: 1841-1850.
15. Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP. Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals. Studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 1994; 170: 414-423.
16. Iwatsubo T, Hirota N, Ooie T et al. Prediction of in vivo drug metabolism in the human liver from in vitro metabolism data. Pharmacol Ther 1997; 73: 5147-5171.
17. Wester MR, Lasker JM, Johnson EF, Raucy JL. CYP2C19 participates in tolbutamide hydroxylation by human liver microsomes. Drug Metab Dispos 2000; 28: 354-359.
18. Rodrigues AD. Integrated cytochrome P450 reaction phenotyping: attempting to bridge the gap between cDNA-expressed cytochromes P450 and native human liver microsomes. Biochem Pharmacol 1999; 57: 465-480.
19. Carlile DJ, Stevens AJ, Ashforth EIL, Waghela D, Houston JB. In vivo clearance of ethoxycoumarin and its prediction from in vitro systems. Use of drug depletion and metabolite formation methods in hepatic microsomes and isolated hepatocytes. Drug Metab Dispos 1998; 26: 216-221.
20. Suzuki A, Iida I, Tanaka F et al. Identification of human cytochrome P-450 isoforms involved in metabolism of R(+)-and S(-)-gallopamil: Utility of in vitro disappearance rate. Drug Metab Dispos 1999; 27: 1254-1259.
21. Waxman DJ, Attisano C, Guengerich FP, Lapenson DP. Human liver microsomal steroid metabolism: identification of the major microsomal steroid hormone 6 beta-hydroxylase cytochrome P-450 enzyme. Arch Biochem Biophys 1988; 263: 424-436.
22. Stormer E, Von Moltke LL, Greenblatt DJ. 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 2000; 295: 793-801.
23. 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.
24. Venkatakrishnan K, Von Moltke LL, Court MH, Harmatz JS, Crespi CL, Greenblatt DJ. 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.
25. Yu A, Haining R. Comparative contribution to dextromethorphan metabolism by cytochrome P450 isoforms in vitro. Can dextromethorphan be used as a dual probe for both CYP2D6 and CYP3A activities? Drug Metab Dispos 2001; 29: 1514-1520.
26. 5 in bacterial membranes. Drug Metab Dispos 1999; 27: 999-1004.
27. Shou M, Lu T, Krausz W et al. Use of inhibitory monoclonal antibodies to assess the contribution of cytochromes P450 to human drug metabolism. Eur J Pharmacol 2000; 394: 199-209.
28. Yamazaki H, Inoue K, Shaw PM, Checovich WJ, Guengerich FP, Shimada T. Different contributions of cytochrome P450 2C19 and 3A4 in the oxidation of omeprazole by human liver microsomes: effects of contents of these two forms in individual human samples. J Pharmacol Exp Ther 1997; 283: 434-442.
29. Lasker JM, Wester MR, Aramsombatdee E, Raucy JL. Characterization of CYP2C19 and CYP2C9 from human liver: respective roles in microsomal tolbutamide, S-mephenytoin, and omeprazole hydroxylations. Arch Biochem Biophys 1998; 353: 16-28.