Pharmacokinetics of 3-keto-desogestrel and ethinylestradiol released from different types of contraceptive vaginal rings.
Pharmacokinetics of 3-keto-desogestrel and ethinylestradiol released from contraceptive vaginal rings (CVRs) with different release rates (75/15, 100/15 and 150/15 micrograms 3-keto-desogestrel/ethinylestradiol daily) were investigated in two studies in young healthy female volunteers. As reference, an oral preparation containing 150 micrograms desogestrel and 30 micrograms ethinylestradiol (MarvelonR tablets) was also administered to the volunteers. To assess the disposition parameters of 3-keto-desogestrel and ethinylestradiol, some of the volunteers were additionally given an i.v. preparation containing 150 micrograms 3-keto-desogestrel and 30 micrograms ethinylestradiol. Serum levels obtained with CVRs showed an initial increase during the first three days, followed by a plateau decreasing only slightly during the remainder of the treatment period. Mean plateau levels (+/- s.d.) of 3-keto-desogestrel were 2.3 +/- 0.9, 2.8 +/- 1.1 and 3.8 +/- 1.1 pmol/ml for CVR 75/15, 100/15 and 150/15, respectively. Mean plateau levels of ethinylestradiol were 184 +/- 75, 262 +/- 102 and 233 +/- 102 pmol/l, respectively. The in vivo release rates of 3-keto-desogestrel and ethinylestradiol from the CVRs were in good agreement with the in vitro release rates. For both steroids the bioavailability from the CVRs was approximately 1.2 times higher than that from the tablets. The 3-keto-desogestrel serum levels were found directly proportional to the release rates within the range studied (75-150 micrograms/day). For ethinylesteradiol the intra-individual variation in steady-state levels was too large to draw pertinent conclusions.
Timmer
C J
CJ
Scientific Development Group, Organon International B.V., Oss, The Netherlands.
Apter
D
D
Voortman
G
G
D000284:Administration, Oral; D000328:Adult; D003274:Contraceptive Devices, Female; D017135:Desogestrel; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008657:Metabolic Clearance Rate; D009652:Norpregnenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D045167:Progesterone Congeners / Q000008:administration & dosage / Q000493:pharmacokinetics; D011863:Radioimmunoassay
D009652:Norpregnenes; D045167:Progesterone Congeners; C044815:etonogestrel; D004997:Ethinyl Estradiol; D017135:Desogestrel