In vitro metabolism of chloroquine: Identification of CYP2C8, CYP3A4, and CYP2D6 as the main isoforms catalyzing N-desethylchloroquine formation

Drug Metabolism and Disposition

Volumn 31, Issue 6, 2003, Pages 748-754

  Projean, Denis ^a,b   Baune, Bruno ^c   Farinotti, Robert ^c   Flinois, Jean Pierre ^d   Beaune, Philippe ^d   Taburet, Anne Marie ^e   Ducharme, Julie ^a,b  

^a UNIVERSITÉ DE MONTRÉAL   (Canada)

^b ASTRAZENECA   (United Kingdom)

^c UNIVERSITÉ PARIS SACLAY   (France)

^d INSERM   (France)

^e BICÊTRE HOSPITAL   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIMALARIAL AGENT; CHLOROQUINE; COMPLEMENTARY DNA; COUMARIN; CYTOCHROME P450; CYTOCHROME P450 2C8; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; DEETHYLCHLOROQUINE; DIETHYLDITHIOCARBAMIC ACID; DRUG METABOLITE; FURAFYLLINE; KETOCONAZOLE; MEPHENYTOIN; QUERCETIN; QUINIDINE; SULFAPHENAZOLE; TROLEANDOMYCIN;

ANIMAL CELL; ARTICLE; BINDING AFFINITY; BIOTRANSFORMATION; CATALYSIS; DRUG HYDROXYLATION; DRUG METABOLISM; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME KINETICS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN TISSUE; INSECT CELL; LIVER MICROSOME; MASS SPECTROMETRY; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL;

ANIMALIA; INSECTA;

EID: 0037518218     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: 10.1124/dmd.31.6.748     Document Type: Article

References (43)

1. Adedoyin A, Frye RF, Mauro K, and Branch RA (1998) Chloroquine modulation of specific metabolizing enzymes activities: investigation with selective five drug cocktail. Br J Clin Pharmacol 46:215-219.
2. Adelusi SA and Salako LA (1982) Tissue and blood concentrations of chloroquine following chronic administration in the rat. J Pharm Pharmacol 34:733-735.
3. Augustjins P, Geusens P, and Verbeke N (1992) Chloroquine levels in blood during chronic treatment of patients with rheumatoid arthritis. Eur J Clin Pharm 42:429-433.
4. Baldwin SJ, Clarke SE, and Chenery RJ (1999) Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of rosiglitazone. Br J Clin Pharmacol 48:424-432.
5. Baune B, Furlan V, Taburet AM, and Farinotti R (1999) Effect of selected antimalarial drugs and inhibitors of cytochrome P-450 3A4 on halofantrine metabolism by human liver microsomes. Drug Metab Dispos 27:565-568.
6. Carlile DJ, Zomorodi K, and Houston JB (1997) Scaling factors to relate drug metabolic clearance in hepatic microsomes, isolated hepatocytes and the intact liver: studies with induced livers involving diazepam. Drug Metab Dispos 25:903-911.
7. Clarke SE (1998) In vitro assessment of human cytochrome P450. Xenobiotica 28:1167-1202.
8. Crespi CL (1995) Xenobiotic-metabolizing human cells as tools for pharmacological and toxicological research. Adv Drug Res 26:179-235.
9. De Vries PJ, Oosterhuis B, and Van Boxtel CJ (1994) Single-dose pharmacokinetics of chloroquine and its main metabolite in healthy volunteers. Drug Investig 8:143-149.
10. Ducharme J and Farinotti R (1996) Clinical pharmacokinetics and metabolism of chloroquine. Focus on recent advancements. Clin Pharmacokinet 31:257-274.
11. Ducharme J and Farinotti R (1997) Rapid and simple method to determine chloroquine and its desethylated metabolites in human microsomes by high-performance liquid chromatography with fluorescence detection. J Chromatogr B 698:243-250.
12. Eagling VA, Tjia JF, and Baek DJ (1998) Differential selectivity of cytochrome P450 inhibitors against probe substrates in human and rat liver microsomes. Br J Clin Pharmacol 45:107-114.
13. Ette EJ, Essien EE, Thomas WO, and Brown-Awala EA (1989) Pharmacokinetics of chloroquine and some of its metabolites in healthy volunteers: a single dose study. J Clin Pharmacol 29:457-462.
14. Frisk-Holmberg M, Bergqvist Y, and Domeij-Nyberg B (1983) Steady-state disposition of chloroquine in patients with rheumatoid disease. Eur J Clin Pharmacol 24:837-839.
15. Frisk-Holmberg M, Bergqvist Y, Termond E, and Domeij-Nyberg B (1984) The single dose kinetics of chloroquine and its major metabolite desethylchloroquine in healthy subjects. Eur J Clin Pharmacol 26:521-530.
16. Grundmann M, Mikulikova I, and Vrublovsky P (1971) Tissue distribution of subcutaneously administered chloroquine in the rat. Arzneim Forsch 21:573-574.
17. Gustafsson LL, Walker O, Alvan G, Beermann B, Estevez F, Gleisner L, Lindstrom B, and Sjoqvist F (1983) Disposition of Chloroquine in man after single intravenous and oral doses. Br J Clin Pharmacol 15:471-479.
18. Halliday RC, Jones BC, Smith DA, Kitteringham NR, and Park BK (1995) An investigation of the interaction between halofantrine, CYP2D6 and CYP3A4: studies with human liver microsomes and heterologous enzyme expression systems. Br J Clin Pharmacol 40:369-378.
19. Houston JB and Kenworthy KE (2000) In vitro-in vivo scaling of CYP kinetic data not consistent with the classical Michaelis-Menten model. Drug Metab Dispos 28:246-254.
20. Lancaster DL, Adio RA, Tai KK, Simooya OO, Broadhead GD, Tucker GT, and Lennard MS (1990) Inhibition of metoprolol metabolism by chloroquine and other antimalarial drugs. J Pharm Pharmacol 34:733-735.
21. Li XQ, Bjorkman A, Andersson TB, Ridderstrom M, and Masimirembwa CM (2002) Amodiaquine clearance and its metabolism to N-desethylamodiaquine is mediated by CYP2C8: a new high affinity and turnover enzyme-specific probe substrate. J Pharmacol Exp Ther 300:399-402.
22. Loft S, Otton V, Lennard M, Tucher G, and Poulsen H (1991) Characterisation of metronidazole metabolism by human liver microsomes. Biochem Pharmacol 41:1127-1134.
23. MacKenzie AH (1983) Pharmacologic actions of 4-aminoquinoline compounds. Am J Med 75 (Suppl 1):5-10.
24. Maksymowych W and Russel AS (1987) Antimalarials in rheumatology: efficacy and safety. Semin Arthritis Rheum 16:206-221.
25. Masimirembwa CM, Hasler JA, and Johansson I (1995) Inhibitory effects of antiparasitic drugs on cytochrome P450 2D6. Eur J Clin Pharmacol 48:35-38.
26. McChesney EW, Fasco MG, and Banks WF (1967) The metabolism of Chloroquine in man during and after repeated oral dosage. J Pharmacol Exp Ther 158:323-331.
27. Muck W (2000) Clinical pharmacokinetics of cerivastatin. Clin Pharmacokinet 39:99-116.
28. Nampoory MR, Nessim J, Gupta KA, and Johny KV (1992) Drug interaction of chloroquine with cyclosporin. Nephron 62:108-109.
29. Newton DJ, Wang RW, and Lu AY (1995) Cytochrome P450 inhibitors. Evaluation of specificities in the in vitro metabolism of therapeutic agents by human liver microsomes. Drug Metab Dispos 23:154-158.
30. 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.
31. Ong CE, Coulter S. Birkett DJ, Bhasker CR, and Miners JO (2000) The xenobiotic inhibitor profile for cytochrome P4502C8. Br J Clin Pharmacol 50:573-580.
32. Pastrakuljic A, Tang BK, Roberts EA, and Kalow W (1997) Distinction of CYP1A1 and CYP1A2 activity by selective inhibition using fluvoxamine and isosafrole. Biochem Pharmacol 53:531-538.
33. Pearce R, Greenway D, and Parkinson A (1992) Species differences and interindividual variation in liver microsomal cytochrome P4502A enzymes: effect on coumarin, dicumarol and testosterone oxidation. Arch Biochem Biophys 298:211-225.
34. Rahman A, Korzekwa KR, Grogan J, Gonzales FJ, and Harris JW (1994) Selective biotransformation of Taxol to 6-alpha hydroxy Taxol by human cytochrome P450 2C8. Cancer Res 54:5543-5546.
35. Robinson AE, Coffer AI, and Camps FE (1970) The distribution of chloroquine in man after fatal poisoning. J Pharm Pharmacol 22:700-703.
36. Simooya OO, Sijumbil G, Lennard MS, and Tucker GT (1998) Halofantrine and Chloroquine inhibit CYP2D6 activity in healthy Zambians. Br J Clin Pharmacol 45:315-317.
37. Strömer E, Von Moltke LL, Shader RI, and Greenblatt DJ (2000) Metabolism of the antidepressant mirtazapine in vitro: contribution of cytochrome P450 1A2, 2D6 and 3A4. Drug Metab Dispos 28:1168-1175.
38. Tiberghien F and Loor F (1996) Ranking of P-glycoprotein substrates and inhibitors by a calcein-AM fluorometry screening assay. Anticancer Drugs 7:568-578.
39. Tsuji A and Tamai Y (1996) Carrier-mediated intestinal transport of drugs. Pharm Res (NY) 13:963-977.
40. Von Moltke LL, Greenblatt DJ, Cotreau-Bibbo MM, Harmatz JS, and Shader RI (1994) Inhibitors of alprazolam metabolism in vitro: effect of serotonin-reuptake-inhibitor antidepressants, ketoconazole and quinidine. Br J Clin Pharmacol 38:23-31.
41. Walker O, Birkett DJ, Alvan G, Gustafsson LL, and Sjoqvist F (1983) Characterization of chloroquine plasma protein binding in man. Br J Clin Pharmacol 15:375-377.
42. Waxman DJ, Lapenson DP, Aoyama T, Gelboin HV, Gonzalez FJ, and Korzekwa K (1991) Steroid hormone hydroxylase specificities for eleven cDNA-expressed human liver cytochrome P450s. Arch Biochem Biophys 290:160-166.
43. Zhao XJ and Ishizaki T (1997) The in vitro hepatic metabolism of quinine in mice, rats and dogs: comparison with human liver microsomes. J Pharmacol Exp Ther 283:1168-1176.