Absolute bioavailability of mianserin tablets and solution in healthy humans

SUMMARY

A pharmacokinetic study with mianserin.HC1 was performed in six healthy male subjects. The subjects were treated on different occasions intravenously with a constant-rate infusion of 5 mg mianserin. HC1 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 I 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 1 h⁻¹ (mean± SEM), the kinetic volume of distribution 444± 250 I, the steady-state volume of distribution 242± 171 1 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± ng · ml⁻¹ and for the tablets 54± 5 ng · 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. The maximum anticipated oral availability determined by hepatic first-pass elimination and taking into account absorption losses was calculated to be in the range of 34–49%.The relatively low extent of absorption can be partially accounted for by firstly an incomplete absorption from the gastro-intestinal tract, which accounts for a loss not exceeding 28% of the dose and secondly a hepatic first-pass effect, which causes approximately 32% of the amount passing through the intestinal wall to be lost before reaching the systemic circulation. The 30 mg tablets were found to be bioequivalent to the oral solution with respect to the extent of absorption as well as the rate of absorption characterized by peak concentration, peak time and absorption half-life.