Role of human liver microsomal CYP3A4 and CYP2B6 in catalyzing N- dechloroethylation of cyclophosphamide and ifosfamide

Biochemical Pharmacology

Volumn 59, Issue 8, 2000, Pages 961-972

  Huang, Zeqi ^a   Roy, Partha ^a   Waxman, David J ^a  

^a Boston University   (United States)

Author keywords

Anticancer drug metabolism; Cyclophosphamide; CYP2B6; CYP3A4; Ifosfamide N dechloroethylation; Oxazaphosphorine metabolism

Indexed keywords

CYCLOPHOSPHAMIDE; CYTOCHROME P450 3A4; DEBRISOQUINE 4 HYDROXYLASE; IFOSFAMIDE;

ARTICLE; CATALYSIS; CONTROLLED STUDY; DRUG ACTIVATION; DRUG HYDROXYLATION; DRUG INACTIVATION; DRUG METABOLISM; HUMAN; HUMAN TISSUE; LIVER MICROSOME METABOLISM; PRIORITY JOURNAL;

ANTI-BACTERIAL AGENTS; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS, ALKYLATING; ARYL HYDROCARBON HYDROXYLASES; BINDING, COMPETITIVE; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CYCLOPHOSPHAMIDE; CYTOCHROME P-450 ENZYME SYSTEM; DNA, COMPLEMENTARY; FLUOROMETRY; HUMANS; IFOSFAMIDE; KINETICS; MICROSOMES, LIVER; MIXED FUNCTION OXYGENASES; OXIDOREDUCTASES, N-DEMETHYLATING; RECOMBINANT PROTEINS; TROLEANDOMYCIN;

EID: 0033951849     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0006-2952(99)00410-4     Document Type: Article

References (39)

1. Fleming R.A. An overview of cyclophosphamide and ifosfamide pharmacology. Pharmacotherapy. 17:1997;146S-154S.
2. Sladek N.E. Metabolism and pharmacokinetic behavior of cyclophosphamide and related oxazaphosphorines. Powers G. Anticancer Drugs Reactive Metabolism and Interactions . 1994;79-156 Pergamon Press, Oxford.
3. Dechant K.L., Brogden R.N., Pilkington T., Faulds D. Ifosfamide/mesna A review of its antineoplastic activity, pharmacokinetic properties and therapeutic efficacy in cancer . Drugs. 42:1991;428-467.
4. Springate J.E. Ifosfamide metabolite chloroacetaldehyde causes renal dysfunction in vivo. J Appl Toxicol. 17:1997;75-79.
5. Pohl J., Stekar J., Hilgard P. Chloroacetaldehyde and its contribution to urotoxicity during treatment with cyclophosphamide or ifosfamide. An experimental study. Arzneimittelforschung. 39:1989;704-705.
6. Zamlauski-Tucker M.J., Morris M.E., Springate J.E. Ifosfamide metabolite chloroacetaldehyde causes Fanconi syndrome in the perfused rat kidney. Toxicol Appl Pharmacol. 129:1994;170-175.
7. Sood C., O'Brien P.J. 2-Chloroacetaldehyde-induced cerebral glutathione depletion and neurotoxicity. Br J Cancer. 74:(Suppl 27):1996;S287-S293.
8. Thigpen T. Ifosphamide-induced central nervous system toxicity. Gynecol Oncol. 42:1991;191-192.
9. Kaijser G.P., Korst A., Beijnen J.H., Bult A., Underberg W.J. The analysis of ifosfamide and its metabolites. Anticancer Res. 13:1993;1311-1324.
10. Kaijser G.P., Beijnen J.H., Bult A., Underberg W.J. Ifosfamide metabolism and pharmacokinetics. Anticancer Res. 14:1994;517-531.
11. Alarcon R.A. Fluorometric determination of acrolein and related compounds with m-aminophenol. Anal Chem. 40:1968;1704-1708.
12. Bohnenstengel F., Eichelbaum M., Golbs E., Kroemer H.K. High-performance liquid chromatographic determination of acrolein as a marker for cyclophosphamide bioactivation in human liver microsomes. J Chromatogr B Biomed Sci Appl. 692:1997;163-168.
13. Kaijser G.P., Ter Riet P.G., de Kraker J., Bult A., Beijnen J.H., Underberg W.J. Determination of 4-hydroxyifosfamide in biological matrices by high-performance liquid chromatography. J Pharm Biomed Anal. 15:1997;773-781.
14. Wright J.E., Tretyakov O., Ayash L.J., Elias A., Rosowsky A., Frei E. III. Analysis of 4-hydroxycyclophosphamide in human blood. Anal Biochem. 224:1995;154-158.
15. Roy P., Yu L.J., Crespi C.L., Waxman D.J. Development of a substrate-activity based approach to identify the major human liver P450 catalysts of cyclophosphamide and ifosfamide activation based on cDNA-expressed activities and liver microsomal P450 profiles. Drug Metab Dispos. 27:1999;655-666.
16. Clarke L., Waxman D.J. Oxidative metabolism of cyclophosphamide Identification of the hepatic monooxygenase catalysts of drug activation . Cancer Res. 49:1989;2344-2350.
17. m catalysts of cyclophosphamide and ifosfamide activation. Pharmacogenetics. 7:1997;211-221.
18. Chang T.K.H., Weber G.F., Crespi C.L., Waxman D.J. Differential activation of cyclophosphamide and ifosphamide by cytochromes P-450 2B and 3A in human liver microsomes. Cancer Res. 53:1993;5629-5637.
19. Ren S., Yang J.S., Kalhorn T.F., Slattery J.T. Oxidation of cyclophosphamide to 4-hydroxycyclophosphamide and deschloroethylcyclophosphamide in human liver microsomes. Cancer Res. 57:1997;4229-4235.
20. Weber G.F., Waxman D.J. Activation of the anti-cancer drug ifosphamide by rat liver microsomal P450 enzymes. Biochem Pharmacol. 45:1993;1685-1694.
21. Kaijser G.P., Beijnen J.H., Bult A., Wiese G., de Kraker J., Keizer H.J., Underberg W.J. Gas chromatographic determination of 2- and 3-dechloroethylifosfamide in plasma and urine. J Chromatogr. 583:1992;175-182.
22. Ruzicka J.A., Ruenitz P.C. Derivatization-liquid chromatographic assay of chloroacetaldehyde in biological samples. J Chromatogr. 518:1990;385-389.
23. Kaijser G.P., Beijnen J.H., Jeunink E.L., Bult A., Keizer H.J., de Kraker J., Underberg W.J. Determination of chloroacetaldehyde, a metabolite of oxazaphosphorine cytostatic drugs, in plasma. J Chromatogr. 614:1993;253-259.
24. Yu L., Waxman D.J. Role of cytochrome P450 in oxazaphosphorine metabolism. Deactivation via N-dechloroethylation and activation via 4-hydroxylation catalyzed by distinct subsets of rat liver cytochromes P450. Drug Metab Dispos. 24:1996;1254-1262.
25. Ruzicka J.A., Ruenitz P.C. Cytochrome P-450-mediated N-dechloroethylation of cyclophosphamide and ifosfamide in the rat. Drug Metab Dispos. 20:1992;770-772.
26. Walker D., Flinois J.-P., Monkman S.C., Beloc C., Boddy A.V., Cholerton S., Daly A.K., Lind M.J., Pearson A.D.J., Beaune P.H., Idle J.R. Identification of the major human hepatic cytochrome P450 involved in activation and N-dechloroethylation of ifosfamide. Biochem Pharmacol. 47:1994;1157-1163.
27. Huang Z., Waxman D.J. HPLC-fluorescent method to determine chloroacetaldehyde, a neurotoxic metabolite of the anti-cancer drug ifosfamide, in plasma and in liver microsomal incubations. Analyt Biochem. 273:1999;117-125.
28. Yang T.J., Krausz K.W., Shou M., Yang S.K., Buters J.T., Gonzalez F.J., Gelboin H.V. Inhibitory monoclonal antibody to human cytochrome P450 2B6. Biochem Pharmacol. 55:1998;1633-1640.
29. Roy P., Tretyakov O., Wright J., Waxman D.J. Stereoselective metabolism of ifosfamide by human P450s 3A4 and 2B6. Favorable metabolic properties of R-enantiomer. Drug Metab Dispos. 27:1999;1309-1318.
30. Kurowski V., Wagner T. Comparative pharmacokinetics of ifosfamide, 4-hydroxyifosfamide, chloroacetaldehyde, and 2- and 3-dechloroethylifosfamide in patients on fractionated intravenous ifosfamide therapy. Cancer Chemother Pharmacol. 33:1993;36-42.
31. Bohnenstengel F., Hofmann U., Eichelbaum M., Kroemer H.K. Characterization of the cytochrome P450 involved in side-chain oxidation of cyclophosphamide in humans. Eur J Clin Pharmacol. 51:1996;297-301.
32. Yu L.J., Drewes P., Gustafsson K., Brain E.G.C., Hecht J.E.D., Waxman D.J. In vivo modulation of alternative pathways of P450-catalyzed cyclophosphamide metabolism Impact on pharmacokinetics and antitumor activity . J Pharmacol Exp Ther. 288:1999;928-937.
33. Granvil C.P., Ducharme J., Leyland-Jones B., Trudeau M., Wainer I.W. Stereoselective pharmacokinetics of ifosfamide and its 2- and 3-N-dechloroethylated metabolites in female cancer patients. Cancer Chemother Pharmacol. 37:1996;451-456.
34. Shimada T., Yamazaki H., Mimura M., Inui Y., Guengerich F.P. 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. 270:1994;414-423.
35. Ekins S., Vandenbranden M., Ring B.J., Gillespie J.S., Yang T.J., Gelboin H.V., Wrighton S.A. Further characterization of the expression in liver and catalytic activity of CYP2B6. J Pharmacol Exp Ther. 286:1998;1253-1259.
36. Code E.L., Crespi C.L., Penman B.W., Gonzalez F.J., Chang T.K., Waxman D.J. Human cytochrome P4502B6, Interindividual hepatic expression, substrate specificity, and role in procarcinogen activation. Drug Metab Dispos. 25:1997;985-993.
37. Wainer I.W., Granvil C.P., Wang T., Batist G. Efficacy and toxicity of ifosfamide stereoisomers in an in vivo rat mammary carcinoma model. Cancer Res. 54:1994;4393-4397.
38. Kurowski V., Cerny T., Kupfer A., Wagner T. Metabolism and pharmacokinetics of oral and intravenous ifosfamide. J Cancer Res Clin Oncol. 117:1991;S148-S153.
39. Lu H., Chan K.K. Differential in vitro hepatic and intestinal metabolism of ifosfamide in the rat. Xenobiotica. 28:1998;779-784.