The relative bioavailability of levonorgestrel and ethinylestradiol when administered in tablet and capsule form

Two low-dose oral contraceptives, both containing the same dose of ethinyl estradiol (EE₂) but different progestins (gestodene and desogestrel, respectively), were compared with respect to the relative bioavailability of EE₂. The study was conducted with 31 women as an open intraindividual comparison with the ingestion of both preparations for 3 months, respectively. On days 1,10 and 21 of the 1 st, 3rd and 6th cycle, blood was sampled at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 h following administration. The concentrations of EE₂ were determined in the serum samples of each individual and the area under the serum concentration versus time curves, AUC (0–4 h) and AUC (0–24 h), were calculated. Corresponding parameters obtained on days 1,10 and 21 of the 3rd and 6th month of treatment were compared on a statistical basis, and no differences were found. This result was in concordance with a previously performed study, where both formulations were administered to 18 women in a single-dose cross-over design. However, the results of the previous and the present study are at variance with the result of one other study, reporting higher EE₂ levels in the serum of women taking the gestodene-containing formulation as compared to those taking the desogestrel-containing formulation.

Section: Discussionsupporting

confidence: 81%

Concentration of Ethinyl Estradiol in the Serum of 31 Young Women following a Treatment Period of 3 Months with Two Low-Dose Oral Contraceptives in an Intraindividual Cross-Over Design

Kuhnz¹,

Back

Power

et al. 1991

“…The results clearly show that there are no differences in systemic EE2 availability between both groups of oral contraceptive users. The SDsof AUCo-4 h in both groups were 115-139 pg-h-mH and thereby in concordance with earlier observations [9], In line with the identical estrogenicity of both prepara tions, no differences in CBG levels could be demon strated.…”

Section: Discussionsupporting

confidence: 78%

“…On an average of 18 plasma concentration-time curves [9], a coefficient of variance of about 35% was found for the most stable parameter (AUC). To detect a difference of mean AUC values of 40, 50 or 60% between two preparations or treatments, 30, 18 or 12 women per group must be inves tigated (a = 0.05, (3 = 0.1), respectively.…”

Section: Discussionmentioning

confidence: 99%

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Comparison of Serum Ethinyl Estradiol, Sex-Hormone-Binding Globulin, Corticoid-Binding Globulin and Cortisol Levels in Women Using Two Low-Dose Combined Oral Contraceptives

Hümpel¹,

Täuber²,

Kuhnz³

et al. 1990

The study included 69 women taking a desogestrel (n = 30)- or gestodene (n = 39)-containing low-dose combined oral contraceptive for at least 3 months. Group size was calculated to detect a difference in mean values of 80% of 1 standard deviation (α = 0.05, β = 0.1). Seven serum samples were obtained up to 4 h, and 1 sample 24 h, after drug intake on 1 day between the 10th and the 21st day of the cycle. The concentrations of sex-hormone-binding globulin (SHBG), corticoid-binding globulin (CBG) and cortisol were measured in a 0- to 4-hour serum pool by radioimmunoassay. Ethinyl estradiol (EE₂) levels were analyzed in single and pooled samples using anti-EE₂-6β-carboxymethyloxime-bovine serum albumin antiserum. The area under the curves (AUC) up to 4 and 24 h and C_maxand t_max were evaluated. Statistical analysis (analysis of covariance) did not reveal a dependence of values on duration of treatment or day of cycle. Both treatments resulted in almost identical values for all parameters evaluated. The mean levels of SHBG, CBG and cortisol were in the range of 186-226nmol/l, 89-93 mg/l and 280- 281 µg/l, respectively. Mean maximum EE₂ levels of 106-129 pg/ml were found 1.6-1.8 h after pill intake and AUC0-4 h accounted for 329-374 pg·h·ml^-1. The recently reported differences in serum EE₂ and CBG levels between two groups of 11 women each treated with desogestrel- and gestodene-containing pills, respectively, could not be confirmed.

“…Pharmacokinetic parameters of LNG determined on day 21 of treatment were in good agreement with those reported recently in a study including 8 Japanese women who received the same triphasic preparation over one treatment cycle [5], Since in both studies, terminal halflife determination of LNG was based on concentration values determined up to 48 h postadministration, the half-life values of approximately 22 h (former study) or 28 h in the present study were about twice as high as corresponding values based on LNG concentrations, de termined only up to 24 h after drug intake [2][3][4], but in keeping with another study [7], where LNG levels were followed up to 72 h postadministration.…”

Section: Discussionsupporting

confidence: 58%

Pharmacokinetics of Levonorgestrel in 18 Women after 1 Month of Treatment with a Triphasic Oral Contraceptive

Kuhnz¹,

Al-Yacoub²

1991

A triphasic levonorgestrel (LNG)- and ethinylestradiol-containing oral contraceptive was administered to 18 women. Plasma samples were obtained throughout a treatment cycle just before drug administration and on the last treatment day (day 21), several plasma samples were collected from each individual up to 48 h postadministration. LNG was determined by radioimmunoassay in all plasma samples. In addition, the concentration of sex-hormone-binding globulin (SHBG) was determined in plasma samples collected from the same subjects during treatment, as well as during a pre- and a posttreatment cycle. During the treatment cycle, plasma levels of LNG determined just before drug administration increased and reached steady state at about day 16. This increase was due to an increased dose of LNG according to the triphasic dose regimen, a concomitantly ethinylestradiol-induced increase in SHBG and due to pharmacokinetic accumulation, since LNG had a terminal half-life of approximately 28.5 h and the dosing interval was 24 h. Steady-state levels and pharmacokinetic parameters of LNG determined on the last day of treatment were in good accordance with previously published results.