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

✍ Scribed by G. Voortman; J. E. Paanakker

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 993 KB
• Volume: 10
• Category: Article
• ISSN: 0885-6222
• DOI: 10.1002/hup.470100803

✦ Synopsis

The absolute bioavailability of mirtazapine, the active constituent of Remerona 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 3.5mg of mirtazapine labelled with the stable isotope carbon-13 was administered concomitantly with an oral dose of 15mg of mirtazapine in the form of standard Remerona tablets. Plasma samples were analysed by GC-MS for non-labelled and 13C-labeIled mirtazapine. Means f standard deviations of pharmacokinetic parameters upon single dosing (and in parentheses at steady state) were as follows: Peak time 1.8 f 0.7 (1 -5 f 0.7) h; Peak level 32 f 13 (42 f 8) ng mi-]; Area under the oral curve 2163t46 (252f48)ngml-I h; Area under the intravenous curve 101 f 11 (124% 19)ngml-I h; Half-life oral 16.3 f 4.6 (16.7 f 5.0) h; Half-life intravenous 9.2 f 4.6 (12.0 3t 5-9) h, probably underestimated. At steady state the trough level was 4-2 f 1-5 ngml-I and the peak-tetrough ratio was 10.6f 5.2. The absolute bioavailability upon single dosing was 50 f 8%, which was not significantly different from the bioavailability at steady state (48 f 7%). These values closely correspond to the maximum attainable bioavailability of 56% for this pharmacokinetic profile.