The pharmacokinetics of ethynylestradiol in the presence and absence of gestodene and desogestrel.
Single doses of ethynylestradiol (30 micrograms) were given alone and in combination with either gestodene (75 micrograms) or desogestrel (150 micrograms) to 10 healthy female volunteers. The doses of steroids were given both orally and by i.v. infusion over 5-7 minutes. Blood samples were taken at regular intervals over 24 hours. The area under the plasma concentration versus time curve (AUC) for oral EE2 alone was 867 +/- 338 pg/ml x h, for oral EE2 in the presence of gestodene it was 795 +/- 206 pg/ml x h and for oral EE2 in the presence of desogestrel it was 614 +/- 132 pg/ml x h. With either gestodene or desogestrel present, the AUC of EE2 was not significantly different from that found when EE2 was given alone. In addition, there was no significant difference between EE2 + gestodene and EE2 + desogestrel. Comparing the relative oral and iv doses, the bioavailability of EE2 (alone) was 59.0 +/- 13% (n = 6), for EE2 plus gestodene it was 62.1 +/- 10% and for EE2 in the presence of desogestrel it was 62.1 +/- 4.4%. The clearance of EE2 (alone) was 19.9 +/- 5.5 l/h and in the presence of gestodene it was 19.4 +/- 9.6 l/h. The clearance of EE2 in the presence of desogestrel appeared slightly greater at 27.7 +/- 8.9 l/h but none of these clearance values were significantly different from each other. The urinary excretion of 6-beta-hydroxy cortisol was similar after all 6 doses of EE2. These data strongly suggest that following single dose administration, neither gestodene nor desogestrel have any inhibitory effect on the metabolism of EE2 or alter its kinetics to any clinically significant extent.
Orme
M
M
Department of Pharmacology and Therapeutics, University of Liverpool, U.K.
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D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D001682:Biological Availability; D017135:Desogestrel; D004338:Drug Combinations; D004347:Drug Interactions; D004997:Ethinyl Estradiol / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000652:urine; D007262:Infusions, Intravenous; D008657:Metabolic Clearance Rate; D009652:Norpregnenes / Q000494:pharmacology*; D045167:Progesterone Congeners / Q000494:pharmacology*; D011863:Radioimmunoassay
D004338:Drug Combinations; D009652:Norpregnenes; D045167:Progesterone Congeners; C033273:Gestodene; D004997:Ethinyl Estradiol; C001380:6 beta-hydroxycortisol; D017135:Desogestrel; D006854:Hydrocortisone