alexa Pharmacokinetics and protein binding of gestodene under treatment with a low-dose combination oral contraceptive for three months.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Bioequivalence & Bioavailability

Author(s): Dibbelt L, Knuppen R, Kuhnz W, Jtting G

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Abstract The serum concentrations of gestodene (CAS 60282-87-3) as well as the binding of this progestin to serum proteins were studied in 40 women who took a low-dose oral contraceptive (Femovan, Femodene) containing 30 micrograms ethinyl estradiol (CAS 57-63-6) and 75 micrograms gestodene for 3 months. On days 1, 10, and 21 of the first and the third treatment cycle, respectively, 7 blood samples were drawn before and up to 4 h after pill intake; additional samples were taken prior to morning ingestion of pill on days 2, 5, 11, 15 and 22 of these cycles. Gestodene levels were measured by means of a specific radioimmunoassay and were evaluated for Cmax, tmax, and AUC up to 4 and 24 h. Independent of the test day and the treatment cycle studied, mean maximum gestodene serum levels were found about 0.8 to 0.9 h after pill intake. During the first treatment cycle, mean values of Cmax, AUC(0-4h), and AUC(0-24h) amounted to 4.3 ng.ml-1, 9.3 ng.ml-1.h, and 27.3 ng.ml-1.h on test day 1; these values increased by 250-400\% and by 300-500\%, respectively, when days 10 and 21 were compared to day 1. On day 1 of the third treatment cycle, these pharmacokinetic parameters were higher by almost a factor of two as compared to the corresponding data obtained on the beginning of the first cycle whereas the increase of these values between day 1 and the subsequent test days (200-300\%) was slightly lower in cycle 3 as compared to cycle 1.(ABSTRACT TRUNCATED AT 250 WORDS) PIP: In Germany, health workers drew serum samples from 40 healthy young women who used a low dose oral contraceptive (OC) (Femovan, Femodene) with 30 mcg ethinyl estradiol and 75 mcg gestodene for 3 treatment cycles to measure gestodene levels, the free fraction of gestodene, and its distribution over the binding proteins in serum pools from all women. Mean maximum gestodene levels occurred .8 to .9 hours after taking the pill. The mean maximum gestodene level on test day 1 was 4.3 ng ml-1 during the first treatment cycle. This figure increased significantly to 7.4 ng ml-1 during the third cycle. Both day 1 levels were significantly lower than the levels obtained on day 10 (10.4 and 13.1 ng ml-1, respectively) and day 21 (12.1 and 13.4 ng ml-1, respectively). The area under the curve zero to 4 hours after pill intake was 9.3 ng ml-1. These figures rose 250-400\% and 300-500\%, respectively, on days 10 and 21. During the third treatment cycle, figures for days 10 and 21 were somewhat lower than those during the first cycle. 78\% of total gestodene was bound to sex hormone binding globulin (SHBG) and 21\% was bound to albumin on day 1 of the first treatment cycle. Just 1\% of gestodene continued to be free. ON day 21, the fraction of gestodene bound to SHBG rose to 87\%, that bound to albumin was 13\%, and 0.5\% remained free. Gestodene was not redistributed over its binding proteins during the third treatment cycle. These results indicated that pharmacokinetic accumulation and the increase in serum SHBG concentration and binding capacity for gestodene allows researchers to understand changes in gestodene levels during longterm treatment with a low dose OC containing gestodene.
This article was published in Arzneimittelforschung and referenced in Journal of Bioequivalence & Bioavailability

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