MIRTAZAPINE PHARMACOKINETICS WITH 2 DOSAGE REGIMENS AND 2 PHARMACEUTICAL FORMULATIONS

Purpose. To compare, in a clinical study of a special design, the phar macokinetic profile of mirtazapine in 20 young healthy male volunteers on two treatment regimens with homothetic oral tablets at steady stat e: NOCTE (1 X 30 mg at 21.00 h) and BID (15 mg at 21.00 h and 15 mg at 09.00 h). Methods. Pharmacokinetic parameters were calculated from mi rtazapine plasma levels assayed by gas chromatography with nitrogen-se nsitive detection. A special analysis of variance allowed interesting interactions to be distinguished. Results. The steady state was reache d after 4 and 6 days for NOCTE and BID respectively; the difference wa s presumably due to intersubject variability. In accordance with pharm acokinetic theory, the peak-to-trough ratio at steady state was signif icantly lower (twofold) for BID than for NOCTE. Within BID, a small di fference (approx. 10%) was found in the extent of absorption between e vening and morning administration. Although statistically significant, this difference meets strict bioequivalence requirements. The regimen s NOCTE and BID were found to be bioequivalent for the steady-state ar ea-under-the-curve-curve and the peak time. Bioequivalence testing for the peak level was not meaningful due to the difference in dosing reg imens. The observed elimination half-lives of 19.7 +/- 3.0 h and 20.8 +/- 2.7 h (n = 20) for NOCTE and BID, respectively are in agreement wi th previous results. Conclusions. Differences (if any) were found to m eet strict bioequivalence requirements and were so small that they are of no clinical consequence.