The bioavailability of desogestrel/ethinyl estradiol tablets relative to the oral solution.

Two studies were conducted in randomised crossover designs to determine the bioavailability of the tablet components of the 'desogestrel/ethinyl estradiol and ethinyl estradiol regimen (MircetteOE)' relative to an oral solution. The desogestrel/ethinyl estradiol and ethinyl estradiol regimen (28 days) consists of the following treatment: 21 days of a 150microg desogestrel (DSG)/20microg ethinyl estradiol (EE) tablet; 2 days of a lactose/starch tablet (placebo); and 5 days of a 10microg EE tablet. In each study, 20 healthy women were enrolled, received at least one dose of test drug, and were included in the analysis of tolerability; however, only 18 subjects in each study completed both crossover periods and were included in the pharmacokinetic analysis. In study 1, the women each received a total dose of 300microg DSG/40microg EE administered as two combination tablets or solution. The women each received a total dose of 20microg EE administered as two tablets or solution in study 2. Serial blood samples were analysed by radioimunnoassay and pharmacokinetic parameters were estimated from the resulting serum concentration-time profiles. The results of these studies demonstrated that the mean relative bioavailabilities of DSG (measured as 3-keto-DSG, the active metabolite of DSG) and EE from the combination tablet were 100% and 93%, respectively, and that of EE from the EE tablet was 99%. The difference in the extent of absorption for the combination tablet versus the reference solution was small; therefore the performance of both tablet formulations was near optimal. Both tablet formulations were generally well tolerated, with most of the adverse experiences reported being transient and mild.

A controlled study of mianserin in moderately to severely depressed outpatients.

Following a 1-week, single-blind placebo washout, 150 patients were randomized to double-blind treatment with daily doses of either mianserin, 30 mg to 150 mg; amitriptyline, 60 mg to 300 mg; or placebo, 1 to 5 capsules taken at bedtime (qhs). Mianserin and amitriptyline were found to be comparable in efficacy, and both significantly more effective than placebo in the treatment of major depressive illness. Rating instruments, all of which showed significant improvement in the active drug groups over the placebo, included the 17- and 21-item Hamilton Rating Scale for Depression (HAM-D), Montgomery and Asberg Depression Rating Scale (MADRS), Self-rating Depression Scale (SDS) index, and the Clinical Global Impressions (CGI) Severity of Illness and Improvement rating scales. Furthermore, for most efficacy parameters in the efficacy-evaluable group, the earliest statistically significant difference vs. placebo could be observed at Visit 1 for the mianserin patients and at Visit 3 for the amitriptyline patients. The safety profile for mianserin was comparable with placebo with respect to laboratory values, electrocardiogram changes, vital signs, ophthalmologic evaluations, and most adverse clinical experiences. Complaints of somnolence and weight gain were comparable in the amitriptyline and mianserin groups. Mianserin was superior to amitriptyline in terms of vital signs; anticholinergic effects; and complaints of dizziness, dyspepsia, and tremor.