Prediction of drug clearance by glucuronidation from in vitro data: Use of combined cytochrome P450 and UDP-glucuronosyltransferase cofactors in alamethicin-activated human liver microsomes

Drug Metabolism and Disposition

Volumn 37, Issue 1, 2009, Pages 82-89

  Kilford, Peter J ^a   Stringer, Rowan ^b   Sohal, Bindi ^b   Houston, J Brian ^a   Galetin, Aleksandra ^a  

^a UNIVERSITY OF MANCHESTER   (United Kingdom)

^b NOVARTIS HORSHAM RESEARCH CENTRE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ALAMETHICIN; BOVINE SERUM ALBUMIN; BUPRENORPHINE; CARVEDILOL; CODEINE; CYTOCHROME P450; DICLOFENAC; GEMFIBROZIL; GLUCURONOSYLTRANSFERASE; KETOPROFEN; MIDAZOLAM; NALOXONE; RALOXIFENE; ZIDOVUDINE;

ARTICLE; CONTROLLED STUDY; DRUG BINDING; DRUG CLEARANCE; DRUG ELIMINATION; ENZYME SUBSTRATE; GLUCURONIDATION; HUMAN; HUMAN CELL; IN VITRO STUDY; LIVER MICROSOME; PRIORITY JOURNAL;

ALAMETHICIN; CHROMATOGRAPHY, LIQUID; CYTOCHROME P-450 ENZYME SYSTEM; GLUCURONIDES; GLUCURONOSYLTRANSFERASE; HUMANS; MICROSOMES, LIVER; TANDEM MASS SPECTROMETRY;

BOVINAE;

EID: 58149472377     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.108.023853     Document Type: Article

References (37)

1. Baiter ZE, Bayliss MR, Beaune PH, Boobis AR, Carlile DJ, Edwards RJ, Houston JB, Lake BG, Lipscomb JC, Pelkouen OR, et al. (2007) Scaling factors for the extrapolation of in vivo metabolic drug clearance from in vitro data: reaching a consensus on values of human microsomal protein and hepatocellularity per gram of liver. Curr Drug Metab 8:33-45.
2. Blum MR, Liao SH, Good SS, and de Miranda P (1988) Pharmacokinetics and bioavailability of zidovudine in humans. Am J Med 85:189-194.
3. Boase S and Miners JO (2002) In vitro-in vivo correlations for drugs eliminated by glucuronidation: investigations with the model substrate zidovudine. Br J Clin Phannacol 54:493-503.
4. Brown HS, Griffin M, and Houston JB (2007) Evaluation of cryopreserved human hepatocytes as an alternative in vitro system to microsomes for the prediction of metabolic clearance. Drug Metab Dispos 35:293-301.
5. Carlile DJ, Hakooz N, Bayliss MK, and Houston JB (1999) Microsomal prediction of in vivo clearance of CYP2C9 substrates in humans. Br J Clin Pharmacol 47:625-635.
6. Engtrakul JJ, Foti RS, Strelevitz TJ, and Fisher MB (2005) Altered AZT (3′-azido-3′-deoxythymidine) glucuronidation kinetics in liver microsomes as an explanation for underprediction of in vivo clearance: comparison to hepatocytes and effect of incubation environment. Drug Metab Dispos 33:1621-1627.
7. Fisher MB, Campanale K, Ackermann BL, VandenBranden M, and Wrighton SA (2000) In vitro glucuronidation using human liver microsomes and the pore-forming peptide alamethicin. Drug Metab Dispos 28:560-566.
8. Gertz M, Kilford PJ, Houston JB, and Galetin A (2008) Drug lipophilicity and microsomal protein concentration as determinants in the prediction of the fraction unbound in microsomal incubations. Drug Metab Dispos 36:535-542.
9. Houston JB (1994) Utility of in vitro drug metabolism data in predicting in vivo metabolic clearance. Biochem Pharmacol 47:1469-1479.
10. Ito K and Houston JB (2005) Prediction of human drug clearance from in vitro and preclinical data using physiologically based and empirical approaches. Pharm Res 22:103-112.
11. Jones HM and 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.
12. Kiang TK, Ensom MH, and Chang TK (2005) UDP-glucuronosyltransferases and clinical drug-drug interactions. Phannacol Ther 106:97-132.
13. Klieber S, Hugla S, Ngo R, Arabeyre-Fabre C, Meunier V, Sadoun F, Fedeli O, Rival M, Bourrie M, Guillou F, et al. (2008) Contribution of the N-glucuronidation pathway to the overall in vitro metabolic clearance of midazolam in humans. Drug Metab Dispos 36:851-862.
14. Kumar S, Samuel K, Subramanian R, Braun MP, Stearns RA, Chiu SH, Evans DC, and Baillie TA (2002) Extrapolation of diclofenac clearance from in vitro microsomal metabolism data: role of acyl glucuronidation and sequential oxidative metabolism of the acyl glucuronide. J Pharmacol Exp Ther 303:969-978.
15. Kumar V, Wahlstrom JL, Rock DA, Warren CJ, Gorman LA, and Tracy TS (2006) CYP2C9 inhibition: impact of probe selection and pharmacogenetics on in vitro inhibition profiles. Drug Metab Dispos 34:1966-1975.
16. Mackenzie PI, Bock KW, Burchell B, Guillemette C, Ikushiro S, Iyanagi T, Miners JO, Owens IS, and Nebert DW (2005) Nomenclature update for the mammalian UDP glycosyltransferase (UGT) gene superfamily. Pharmacogenet Genomics 15:677-685.
17. Miners JO, Knights KM, Houston JB, and Mackenzie PI (2006) In vitro-in vivo correlation for drugs and other compounds eliminated by glucuronidation in humans: pitfalls and promises. Biochem Pharmacol 71:1531-1539.
18. Miners JO, Smith PA, Sorich MJ, Mc Kinnon RA, and Mackenzie PI (2004) Predicting human drug glucuronidation parameters: application of in vitro and in silico modeling approaches. Annu Rev Pharmacol Toxicol 44:1-25.
19. Mistry M and Houston JB (1987) Glucuronidation in vitro and in vivo: comparison of intestinal and hepatic conjugation of morphine, naloxone. and buprenorphine. Drug Metab Dispos 15:710-717.
20. Mohutsky M, Chien J, Ring B, and Wrighton S (2006) Predictions of the in vivo clearance of drugs from rate of loss using human liver microsomes for phase I and phase II biotransformations. Pharmacol Res 23:654-662.
21. Obach RS (1999) 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 27:1350-1359.
22. Obach RS (2001) The prediction of human clearance from hepatic microsomal metabolism data. Curr Opin Drug Discov Devel 4:36-44.
23. Obach RS, Baxter JG, Liston TE, Silber BM, Jones BC, Maclntyre F, Rance DJ, and Wastall P (1997) The prediction of human pharmacokinetic parameters from preclinical and in vitro metabolism data. J Pharmacol Exp Ther 283:46-58.
24. Ogilvie BW, Zhang D, Li W, Rodrigues AD, Gipson AE, Holsapple J, Toren P, and Parkinson A (2006) Glucuronidation converts gemfibrozil to a potent, metabolism-dependent inhibitor of CYP2C8: implications for drug-drug interactions. Drug Metab Dispos 34:191-197.
25. Picard N, Cresteil T, Djebli N, and Marquet P (2005) In vitro metabolism study of buprenorphine: evidence for new metabolic pathways. Drug Metab Dispos 33:689-695.
26. Rawden HC, Carlile DJ, Tindall A, Hallifax D, Galetin A, Ito K, and Houston JB (2005) Microsomal prediction of in vivo clearance and associated interindividual variability of six benzodiazepines in humans. Xenobiotica 35:603-625.
27. Riley RJ, McGinnity DF, and Austin RP (2005) A unified model for predicting human hepatic, metabolic clearance from in vitro intrinsic clearance data in hepatocytes and microsomes. Drug Metab Dispos 33:1304-1311.
28. Rostami-Hodjegan A and Tucker GT (2007) Simulation and prediction of in vivo drug metabolism in human populations from in vitro data. Nat Rev Drug Discov 6:140-148.
29. Rowland A, Elliot DJ, Knights KM, Mackenzie PL, and Miners JO (2008a) The "albumin effect" and in vitro-in vivo extrapolation: sequestration of long chain unsaturated fatty acids enhances phenytoin hydroxylation by human liver microsomal and recombinant cytochrome P450 2C9. Drug Metab Dispos 36:870-877.
30. Rowland A, Gaganis P, Elliot DJ, Mackenzie PI, Knights KM, and Miners JO (2007) Binding of inhibitory fatty acids is responsible for the enhancement of UDP-glucuronosyltransferase 2B7 activity by albumin: implications for in vitro-in vivo extrapolation. J Pharmacol Exp Ther 321:137-147.
31. Rowland A, Knights KM, Mackenzie PL, and Miners JO (2008b) The "albumin effect" and drug glucurouidation: bovine serum albumin and fatty acid free serum albumin enhance the glucuronidation of UGTLA9 substrates but not UGT1A1 and UGT1A6 activities. Drug Metab Dispos 36:1056-1062.
32. Sheiner LB and Beal SL (1981) Some suggestions for measuring predictive performance. J Pharmacokinet Biopharm 9:503-512.
33. Soars MG, Burchell B, and Riley RT (2002) Ln vitro analysis of human drug glucuronidation and prediction of in vivo metabolic clearance. J Pharmacol Exp Ther 301:382-390.
34. Soars MG, Ring BJ, and Wrighton SA (2003) The effect of incubation conditions on the enzyme kinetics of UDP-glucurouosyltrausferases. Drug Metab Dispos 31:762-767.
35. Spahn-Laugguth H and Benet LZ (1992) Acyl glucuronides revisited: is the glucurouidation process a toxification as well as a detoxification mechanism? Drug Metab Rev 24:5-47.
36. I/AUC) ratios. Drug Metab Dispos 32:1201-1208.
37. Yang J, Jamei M, Yeo KR, Rostami-Hodjegan A, and Tucker GT (2007) Misuse of the well-stirred model of hepatic drug clearance. Drug Metab Dispos 35:501-502.