The role of cyp2c in the in vitro bioactivation of the contraceptive steroid desogestre

Journal of Pharmacology and Experimental Therapeutics

Volumn 287, Issue 3, 1998, Pages 975-982

  Gentile, Daniela M ^a  

^a New Medical Building ^*  (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

3 KETO DESOGESTREL; 3-KETO-DESOGESTREL; CONTRACEPTIVE AGENT; CYP2C19 PROTEIN, HUMAN; CYP2C9 PROTEIN, HUMAN; CYP3A PROTEIN, HUMAN; CYP3A4 PROTEIN, HUMAN; CYTOCHROME P450; DESOGESTREL; ENZYME; ENZYME INHIBITOR; MIXED FUNCTION OXIDASE; ORAL CONTRACEPTIVE AGENT; PROGESTERONE DERIVATIVE; STEROID 16ALPHA MONOOXYGENASE; STEROID MONOOXYGENASE; UNSPECIFIC MONOOXYGENASE; CYTOCHROME P450 2C19; CYTOCHROME P450 2C9; CYTOCHROME P450 3A4; CYTOCHROME P450 ISOENZYME; ETONOGESTREL; MEPHENYTOIN; SULFAPHENAZOLE; UNCLASSIFIED DRUG;

ARTICLE; BIOLOGY; BIOTRANSFORMATION; CELL LINE; CLINICAL RESEARCH; CONTRACEPTION; CONTRACEPTIVE AGENTS, PROGESTIN; DRUG ANTAGONISM; ENZYMES AND ENZYME INHIBITORS; ENZYMOLOGY; FAMILY PLANNING; GENETICS; HUMAN; HYDROXYLATION; IN VITRO STUDY; LIVER MICROSOME; METABOLISM; METHODOLOGY; PHYSIOLOGY; RESEARCH REPORT; DRUG ACTIVATION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN CELL; LIVER MICROSOME METABOLISM; MASS SPECTROMETRY; MICHAELIS CONSTANT; PRIORITY JOURNAL; STEROID METABOLISM;

BIOLOGY; CLINICAL RESEARCH; CONTRACEPTION; CONTRACEPTIVE AGENTS; CONTRACEPTIVE AGENTS, FEMALE; CONTRACEPTIVE AGENTS, PROGESTIN; DESOGESTREL; ENZYMES; ENZYMES AND ENZYME INHIBITORS; FAMILY PLANNING; IN VITRO; PHYSIOLOGY; RESEARCH METHODOLOGY; RESEARCH REPORT;

ARYL HYDROCARBON HYDROXYLASES; BIOTRANSFORMATION; CELL LINE; CONTRACEPTIVES, ORAL, SYNTHETIC; CYTOCHROME P-450 ENZYME SYSTEM; DESOGESTREL; ENZYME INHIBITORS; HUMANS; HYDROXYLATION; MICROSOMES, LIVER; MIXED FUNCTION OXYGENASES; PROGESTERONE CONGENERS; STEROID 16-ALPHA-HYDROXYLASE; STEROID HYDROXYLASES;

EID: 0032239288     PISSN: 00223565     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (31)

1. Abel SM and Back DJ (1993) Cortisol metabolism in vitro-lll. Inhibition of microsomal 6β-hydroxylase and cytosolic 4-ene-reductase. J Steroid Biochem Mol Biol 46:827-832.
2. Aoyama T, Korzekwa K, Nagata K, Gillette J, Gelboin HV and Gonzalez FJ (1990) Estradiol metabolism by complementary deoxyribonucleic acid-expressed human cytochrome P450s. Endocrinology 126:3101-3106.
3. Back DJ, Grimmer SFM, Shenoy N and Orme M L'E (1987) Plasma concentrations of 3-keto-desogestrel after oral administration of desogestrel and intravenous administration of 3-keto-desogestrel. Contraception 35:619-626.
4. Back DJ, Tjia JF, Karbwang J and Colbert J (1988) In vitro inhibition studies of tolbutamide hydroxylase activity of human liver microsomes by azoles, sulphonamides and quinoîines. Br J Clin Pharmacol 26:23-29.
5. Baldwin SJ, Bloomer JC, Smith GJ, Ayrton AD, Clarke SE and Chenery RJ (1995) Ketoconazole and sulphaphenazole as the respective selective inhibitors of P4503A and 2C9. Xenobiotica 25:261-270.
6. Ball SE, Forrester LM, Wolf CR and Back DJ (1990) Differences in the cytochrome P-450 isozymes involved in the 2-hydroxylation of oestradiol and 17ethinyloestradiol. Biochem J 267:221-226.
7. Bergink W, Assendorp R, Kloosterboer L, van Lier W, Voortman G and Qvist I (19901 Serum pharmacokinetics of orally administered desogestrel and binding of contraceptive progestogens to sex hormone-binding globulin. Am J Obstet Gynecol 163:2132-2137.
8. Bhasker CR, Miners JO, Coulter S and Birkett DJ (1997) Allelic and functional variability of cytochrome P4502C9. Pharmacogenetics 7:51-58.
9. Bourrie M, Meunier V, Berger Y and Fabre G (1996) Cytochrome P450 isoform inhibitors as a tool for the investigation of metabolic reactions catalysed by human liver microsomes. J Pharmacol Exp Ther 277:321-332.
10. Eagling VA, Back DJ and Barry MG (1997) Differential inhibition of cytochrome P450 isoforms by the protease inhibitors, ritonavir, saquinavir and indinavir. Br J Clin Pharmacol 44:190-194.
11. Gentile DM, Tomlinson ES, Maggs JL, Park BK and Back DJ (1996) Dexamethasone metabolism by human liver in vitro. Metabolite identification and inhibition of 6-hydroxylation. J Pharmacol Exp Ther 277:105-112.
12. Goldstein JA and Morais SMF de (1994) Biochemistry and molecular biology of the human CYP2C subfamily. Pharmacogenetics 4:285-299.
13. Guengerich FP (1988) Oxidation of 17a-ethinylestradiol by human liver cytochrome P-450. Mol Pharmacol 33:500-508.
14. Guengerich FP and Shimada T (1991) Oxidation of toxic and carcinogenic chemical by human cytochrome P450 enzymes. Chem Res Toxicol 4:391-407.
15. Hasenack HG, Bosch AMG and Kaar K (1986) Serum levels of desogestrel after oral administration of desogestrel and 3-ketodesogestrel. Contraception 33:591-596.
16. Jönsson G, Astrom A and Andersson P (1995) Budesonide is metabolised by cyto-chrome P450 3A (CYP3A) enzymes in human liver. Drug Metab Dispos 23:137-142.
17. Lowry OH, Rosenbrough NJ, Farr AL and Randall RJ (1951) Protein determination with the Folin phenol reagent. J Biol Chem 193:265-275.
18. Madden S, Back DJ and Orme ML'E (1990) Metabolism of the contraceptive steroid desogestrel by human liver in vitro. J Steroid Biochem 35:281-288.
19. Maurice M, Pichard L, Daujat M, Fabre I, Joyeux H, Domergue J and Maurel P (1992) Effects of imidazole derivatives on cytochromes P-450 from human hepatocytes in primary culture. FASEB J 6:752-758.
20. McClamrock HD and Adashi EY (1993) Pharmacokinetics of desogestrel. Am J Obstet Gynecol 168:1021-1028.
21. Ono S, Hatanaka T, Hotta H, Satoh T, Gonzalez FJ and Tsutsui M (1996) Specificity of substrate and inhibitor probes for cytochrome P450s: Evaluation of in vitro metabolism using cDNA-expressed human P450s and human liver microsomes Xenobiotica 26:681-693
22. Peter R, Bocker R, Beaune PH, Iwasaki M, Guengerich FP and Yang CS (1990) Hydroxylation of chlorzoxazone as a specific probe for human liver cytochrom ? P-450IIE1. Chem Res Toxicol 3:566-573.
23. Purba HS, Maggs JL, Orme ML'E, Back DJ and Park BK (1987) The metabolism of 17a-ethyinylestradiol by human liver microsomes: Formation of catechol and chemically reactive metabolites. Br J Clin Pharmacol 23:447-453.
24. Schmider J, Greenblatt DJ, Moltke LL von, Karsov D, Vena R, Friedman HL anil Shader Rl (1997) Biotransformation of mestranol to ethinyloestradiol in vitro: the role of cytochrome P450 2C9 and metabolic inhibitors. J Clin Pharmacol 37:193-200.
25. Viinikka L (1979) Metabolism of a new synthetic progestogen, ORG2969 by human liver in vitro. J Steroid Biochem 10:353-357.
26. Viinikka L, Ylikorkala O, Nummi S, Virkkunen P, Ranta T, Alapiessa U and Vihk ) R (1976) Biological effects of a new and potent progestogen. A clinical study. Acta Endocrinol 83:429-438.
27. Waterman MR, John ME and Simpson ER (1986) Regulation of synthesis and activity of cytochrome P-450 enzymes in physiological pathways, in Cytochrom'. P-450 (de Montelano 0 ed) pp 345-386, Pergamon, New York.
28. Waxman DJ, Attisano C, Guengerich FP and Lapenson DP (1988) Human liver microsomal steroid metabolism. Identification of the major microsomal steroid hormone 6β hydroxylase cytochrome P450 enzyme. Arch Biochem Biophys 263: 424-436.
29. Waxman DJ, Lapenson DP, Aoyama T, Gelboin HV, Gonzalez FJ and Kozelkwa K ( 1991) Steroid hormone hydroxylase specificities of eleven cDNA-expressed human cytochrome P450s. Arch Biochem Biophys 290:160-166.
30. Wienkers LC, Wurden CJ, Storch E, Kunze KL, Rettie AE and Trager WF (1990) Formation of R(8)hydroxywarfarin in human liver microsomes. Drug Metab Dispo-s 24:610-614.
31. Yamazaki H and Shimada T (1997) Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9 and 3A4 in human liver microsomes. Arch Biochem Biophys 346:161-169