BIOAVAILABILITY OF MIRTAZAPINE FROM REMERON(R) TABLETS AFTER SINGLE AND MULTIPLE ORAL DOSING

The absolute bioavailability of mirtazapine, the active constituent of Remeron(R) tablets, a new antidepressant developed under the laborato ry code Org 3770, was assessed in eight healthy young male volunteers after a single oral dose and during multiple oral dosing for seven day s. An intravenous dose of 3.5 mg of mirtazapine labelled with the stab le isotope carbon-13 was administered concomitantly with an oral dose of 15 mg of mirtazapine in the form of standard Remeron(R) tablets. Pl asma samples were analysed by GC-MS for non-labelled and C-13-labelled mirtazapine. Means+/-standard deviations of pharmacokinetic parameter s upon single dosing (and in parentheses at steady state) were as foll ows: 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; Ar ea under the intravenous curve 101+/-11 (124+/-19) ng ml(-1) h; Half-l ife oral 16.3+/-4.6 (16.7+/-5.0) h; Half-life intravenous 9.2+/-4.6 (1 2.0+/-5.9) h, probably underestimated. At steady state the trough leve l 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 wa s 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.