Bioavailability of mirtazapine from Remeron® tablets after single and multiple oral dosing

Abstract

The absolute bioavailability of mirtazapine, the active constituent of Remeron® tablets, a new antidepressant developed under the laboratory code Org 3770, was assessed in eight healthy young male volunteers after a single oral dose and during multiple oral dosing for seven days. An intravenous dose of 3.5 mg of mirtazapine labelled with the stable isotope carbon-13 was administered concomitantly with an oral dose of 15 mg of mirtazapine in the form of standard Remeron® tablets. Plasma samples were analysed by GC-MS for non-labelled and 13C-labelled mirtazapine. Means ± standard deviations of pharmacokinetic parameters upon single dosing (and in parentheses at steady state) were as follows: Peak time 1.8 ± 0.7 (1.5 ± 0.7) h; Peak level 32 ± 13 (42 ± 8) ng ml−1; Area under the oral curve 216 ± 46 (252 ± 48) ng ml−1 h; Area under the intravenous curve 101 ± 11 (124 ± 19) ng ml−1 h; Half-life oral 16.3 ± 4.6 (16.7 ± 5.0) h; Half-life intravenous 9.2 ± 4.6 (12.0 ± 5.9) h, probably underestimated. At steady state the trough level was 4.2 ± 1.5 ng ml−1 and the peak-to-trough ratio was 10.6 ± 5.2. The absolute bioavailability upon single dosing was 50 ± 8%, which was not significantly different from the bioavailability at steady state (48 ± 7%). These values closely correspond to the maximum attainable bioavailability of 56% for this pharmacokinetic profile.