PHARMACOKINETIC DOSE-PROPORTIONALITY STUDY AT STEADY-STATE OF MIRTAZAPINE FROM REMERON(R) TABLETS

Steady-state dose proportionality of mirtazapine, the active constitue nt of Remeron(R) tablets, a new antidepressant developed under the lab oratory code Org 3770, was investigated. Each of 27 young healthy male subjects received a single daily oral dose of mirtazapine in the form of standard Remeron(R) tablets, beginning with 15 mg per day and adva ncing at five-day intervals to the next higher dose. The oral doses of mirtazapine were 15, 30, 45, 60 and 75 mg per day. Serial blood sampl es were taken on the fifth day of each dosing period and at several ot her times in order to check whether the steady state had been reached. In addition, blood samples were taken up to 120 hours after the last dose of 75 mg in order to accurately determine the elimination half-li fe. Plasma levels of mirtazapine were determined by capillary gas chro matography with nitrogen sensitive detection. Pharmacokinetic paramete rs were calculated from the plasma mirtazapine levels and subjected to analysis of variance. The steady state was attained on the fifth day of each dosing period. Pharmacokinetics of mirtazapine was found to be essentially linear in the dose range studied. Mean+/-SD of the elimin ation half-life were accurately determined as 21.5+/-5.0 h (n=27), ran ge 13.1-33.6 h.