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In a three-period cross-over study with 24 healthy young females (study part 1), the bioavailability of etonogestrel (3-ketodesogestrel) was determined after a single oral dose of two Cerazette tablets (each containing 75 microg desogestrel), one Liseta tablet (containing 150 microg desogestrel and 1.5 mg 17beta-estradiol), and an intravenous dose of 150 microg etonogestrel. Etonogestrel serum levels from 23 subjects could be analysed by radio-immunoassay. The geometric mean bioavailability of etonogestrel from Cerazette and Liseta tablets was 0.79 and 0.82, with 95% confidence intervals of 0.73-0.86 and 0.76-0.88, respectively. Also, the oral formulations were found to be bioequivalent. Subsequently, the single-dose pharmacokinetic parameters of etonogestrel from Cerazette tablets were compared with those after multiple dosing of one Cerazette tablet once daily for 7 days, in a subgroup of 12 subjects (study part 2). A steady state was observed from the fourth day of daily dosing onwards, with time-invariant parameters except for a 14% lower dose-normalised AUC. The least-squares geometric means of the elimination half-life of etonogestrel were approximately 30 h for the three single-dose treatments in study part 1, as well as for the single- and multiple-dose treatments of Cerazette in study part 2, without differences between groups.

Objective: The aim of the study was to assess the bioavailability of estradiol (E2) following oral, single-dose administration of equimolar doses of three HRT preparations in a 3-way cross-over study in postmenopausal women., Methods: 18 healthy subjects were enrolled. Free E2 and estrone (E1) serum concentrations were determined using commercially available immunoassay kits. Bioequivalence testing was performed between the following oral formulations: (a) 1.5 mg E2 tablets versus 2 mg E2V tablets; and (b) 1.5 mg E2 plus 0.15 mg DSG tablets versus 1.5 mg E2 tablets., Results: For both E2 and E1 the E2 tablet was bioequivalent with both the E2V and the E2/DSG tablet with respect to the rate and extent of absorption (bioavailability). Although the mean tmax values of the three tablet formulations were similar, the variability was too large to prove formal bioequivalence., Conclusion: E2 tablets and E2/DSG tablets were bioequivalent and also bioequivalence of E2 tablets with commercially available E2V was found, which ensures a sequential HRT preparation without large variations in estrogen serum concentrations.

The effect of a high-fat meal on the pharmacokinetics of mirtazapine was studied in 19 healthy normal young male volunteers. In a randomized two-period crossover study, each volunteer received an oral dose of 15 mg of mirtazapine in the form of tablets, in the fasting state and after a high-fat meal, with a washout period of 14 days between the two doses. Serial blood samples were taken and pharmacokinetic parameters calculated and statistically analyzed from mirtazapine plasma levels. The extent of absorption of mirtazapine, as measured by the area under the plasma level versus time curve, was found to be equivalent for the fasting and the fed state. Food intake was shown to have no influence on the elimination of mirtazapine, as measured by its elimination half-life. The rate of mirtazapine absorption, as measured by the peak level (Cmax), was not altered by food. The peak time (tmax), however, in subjects in the fed state showed an increase: the 90%-confidence interval for the median difference ranged from 0.25 to 1.25 h. This was the only effect of food found in this study. It is considered to be of no clinical consequence.

A pharmacokinetic study with mianserin . HCl was performed in six healthy male subjects. The subjects were treated on different occasions intravenously with a constant-rate infusion of 5 mg mianserin. HCl in 1 h, orally with a single dose of 60 mg as two tablets of 30 mg each and with 60 mg as an oral solution. The wash-out period between treatments was 1 month. Blood samples were taken at predetermined times over a period of 120 h following dosing. The mianserin concentration in the plasma samples was determined and the results were pharmacokinetically analyzed. The intravenous data could be adequately described by a 3-compartment model and the oral data by a 2-compartment model, both with first-order transfer and elimination rate constants. The mean plasma clearance of mianserin was found to be 19 +/- 2 l h-1 (mean +/- SEM), the kinetic volume of distribution 444 +/- 250 l, the steady-state volume of distribution 242 +/- 171 l and the elimination half-life 33 +/- 5 h. The absolute bioavailability in terms of extent of absorption was 22 +/- 3% for the solution and 20 +/- 3% for the tablets. The mean peak level for the solution was 79 +/- 11 ng X ml-1 and for the tablets 54 +/- 5 ng X ml-1; mean peak time for the solution was 1.1 +/- 0.2 h and for the tablets 1.4 +/- 0.2 h. The mean absorption half-life for the solution was 0.43 +/- 0.13 h and for the tablets 0.39 +/- 0.11 h.(ABSTRACT TRUNCATED AT 250 WORDS)