Predicting the oral bioavailability of 19-nortestosterone progestins in vivo from their metabolic stability in human liver microsomal preparations in vitro

Drug Metabolism and Disposition

Volumn 26, Issue 11, 1998, Pages 1120-1127

  Kuhnz, Wilhelm ^a   Gieschen, Hille ^b  

^a BAYER PHARMA AG   (Germany)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

DESOGESTREL; DIENOGEST; ETONOGESTREL; GESTAGEN; GESTODENE; LEVONORGESTREL; NANDROLONE DERIVATIVE; NORETHISTERONE; NORGESTIMATE;

ARTICLE; CORRELATION FUNCTION; DRUG BIOAVAILABILITY; DRUG METABOLISM; DRUG STABILITY; FEMALE; HUMAN; HUMAN TISSUE; IN VITRO STUDY; IN VIVO STUDY; LIVER MICROSOME; MALE; MICHAELIS CONSTANT; ORAL DRUG ADMINISTRATION; PREDICTION; PRIORITY JOURNAL;

BIOLOGICAL AVAILABILITY; FEMALE; HALF-LIFE; HUMANS; MALE; MICROSOMES, LIVER; NANDROLONE; PROGESTERONE CONGENERS;

EID: 0031794065     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (29)

1. Back DJ, Breckenridge AM, Crawford FE, McIver M, Orme MLE, Park BK, Rowe PH and Smith E (1978) Pharmacokinetics of norethindrone in women. 2. Single dose pharmacokinetics. Clin Pharmacol Ther 24:448-453.
2. Back DJ, Breckenridge AM, Gay FE, McIver M, Orme MLE, Park BK, Rowe PH and Smith E (1977) Pharmacokinetics of norethisterone in women. Br J Clin Pharmacol 4:729-730p.
3. Back DJ, Grimmer SFM, Rogers S, Stevenson PJ and Orme MLE (1987a) Comparative pharmacokinetics of levonorgestrel and ethinyloestradiol following intravenous, oral and vaginal administration. Contraception 36:471-479.
4. Back DJ, Grimmer SFM, Shenoy N and Orme MLE (1987b) Plasma concentrations of 3-ketodesogestrel after oral administration of desogestrel and intravenous administration of 3-ketodesogestrel. Contraception 35:619-626.
5. Dibbelt L, Knuppen R, Kuhnz W and Jütting G (1992) Pharmacokinetics and protein binding of gestodene under treatment with a low-dose combination oral contraceptive for three months. Drug Res 42:1146-1152.
6. Hammond GL, Lähteenmäki PLA, Lähteenmäki P and Luukkainen T (1982) Distribution and percentages of non-protein bound contraceptive steroids in human serum. J Steroid Biochem 17:375-380.
7. Heuner A, Kuhnz W, Heger-Mann D, Richert K and Hümpel M (1995) A single-dose and 3-month clinical-pharmacokinetic study with a new combination oral contraceptive. Adv Contracept 11:207-225.
8. Hoener BA (1994) Predicting the hepatic clearance of xenobiotics in humans from in vitro data. Biopharm Drug Dispos 15:295-304.
9. Houston JB (1994) Utility of in vitro drug metabolism data in predicting in vivo metabolic clearance. Biochem Pharmacol 47:1469-1479.
10. Hümpel M, Wendt H, Pommerenke G, Weiss C and Speck U (1987) Investigations of pharmacokinetics of levonorgestrel to specific consideration of a possible first-pass effect in women. Contraception 17:207-220.
11. Kuhnz W, Al-Yacoub G and Fuhrmeister A (1992a) Pharmacokinetics of levonorgestrel and ethinylestradiol in 9 women who received a low-dose oral contraceptive over a treatment period of 3 months and, after a wash-out phase, a single oral administration of the same contraceptive formulation. Contraception 46:455-469.
12. Kuhnz W, Al-Yacoub G and Fuhrmeister A (1992b) Pharmacokinetics of levonorgestrel in 12 women who received a single oral dose of 0.15 mg levonorgestrel and, after a wash-out phase, the same dose during one treatment cycle. Contraception 46:443-454.
13. Kuhnz W, Al-Yacoub G, Power J, Ormesher SE, Back DJ and Jütting G (1992c) Pharmacokinetics and serum protein binding of 3-keto-desogestrel in women during three cycles of treatment with a low-dose combination oral contraceptive. Drug Res 42:1142-1146.
14. Kuhnz W, Baumann A, Staks T, Dibbelt L, Knuppen R and Jütting G (1993) Pharmacokinetics of gestodene and ethinylestradiol in 14 women during three months of treatment with a new tri-step combination oral contraceptive: serum protein binding of gestodene and influence of treatment on free and total testosterone levels in the serum. Contraception 48:303-322.
15. Kuhnz W, Gansau C and Fuhrmeister A (1992d) Pharmacokinetics of gestodene in 12 women who received a single oral dose of 0.075 mg gestodene and, after a wash-out phase, the same dose during one treatment cycle. Contraception 46:20-40.
16. Kuhnz W, Schütt B, Power J and Back DJ (1992e) Pharmacokinetics and serum protein binding of gestodene and 3-keto-desogestrel in women after single oral administration of two different contraceptive formulations. Drug Res 42:1139-1141.
17. Kuhnz W, Schütt B and Woloszczak R (1994a) Influence of changes in the concentration of sex hormone-binding globulin in human serum on the protein binding of the contraceptive steroids levonorgestrel, 3-keto-desogestrel and gestodene. J Steroid Biochem Mol Biol 48:573-580.
18. Kuhnz W, Staks T and Jütting G (1994b) Pharmacokinetics of levonorgestrel and ethinylestradiol in 14 women during three months of treatment with a tri-step combination oral contraceptive: serum protein binding of levonorgestrel and influence of treatment on free and total testosterone levels in serum. Contraception 50:563-579.
19. Lentner C ed (1981) Geigy Scientific Tables, vol 1, p 220, Ciba-Geigy, Basel.
20. Lin JH, Sugiyama Y, Awazu S and Hanano M (1980) Kinetic studies on the deethylalion of ethoxybenzamide: a comparative study with isolated hepatocytes and liver microsomes of rat. Biochem Pharmacol 29:2825-2830.
21. Madden S and Back DJ (1991) Metabolism of norgestimate by human gastrointestinal mucosa and liver microsomes in vitro. J Steroid Biochem Mol Biol 38:497-503.
22. Madden S, Back DJ, Martin CA and Orme MLE (1989) Metabolism of the contraceptive steroid desogestrel by the intestinal mucosa. Br J Clin Pharmacol 27:295-299.
23. Obach RS (1996) The importance of nonspecific binding in in vitro matrices, its impact on enzyme kinetic studies of drug metabolism reactions, and implications for in vitro-in vivo correlations. Drug Metab Dispos 24:1047-1049.
24. Obach RS, Baxter JG, Liston TE, Silber BM, Jones BC, MacIntyre 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.
25. Oettel M, Bervoas-Martin S, Elger W, Golbs S, Hobe G, Kaufmann G, Mathieu M, Moore C, Puri C, Ritter P, Reddersen G, Schön R, Strauch G and Zimmermann H (1995) A 19-norprogestin without a 17α-ethinyl group. I. Dienogest from a pharmacokinetic point of view. Drugs Today 31:499-516.
26. Orme MLE, Back DJ, Ward S and Green S (1991) The pharmacokinetics of ethynylestradiol in the presence and absence of gestodene and desogestrel. Contraception 43:305-316.
27. Rane A, Wilkinson GR and Shand DG (1977) Prediction of hepatic extraction ratio from in vitro measurements of intrinsic clearance. J Pharmacol Exp Ther 200:420-424.
28. Sidelmann UG, Cornett C, Tjornelund J and Hansen SH (1996) A comparative study of precision cut liver slices, hepatocytes, and liver microsomes from the Wistar rat using metronidazole as a model substance. Xenobiotica 26:709-722.
29. Täuber U, Tack JW and Matthes H (1989) Single dose pharmacokinetics of gestodene in women after intravenous and oral administration. Contraception 40:461-479.