caa a22 4500 477125670 CHVBK 20180405111648.0 cr unu---uuuuu 170330e19970101xx s 000 0 eng 10.1023/A:1012067703764 doi (NATIONALLICENCE)springer-10.1023/A:1012067703764 Mirtazapine Pharmacokinetics with Two Dosage Regimens and Two Pharmaceutical Formulations [Elektronische Daten] [Cees Timmer, Jan Paanakker, Maria Vrijmoed-de Vries] Purpose. To compare, in a clinical study of a special design, the pharmacokinetic profile of mirtazapine in 20 young healthy male volunteers on two treatment regimens with homothetic oral tablets at steady state: NOCTE (1 × 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 mirtazapine plasma levels assayed by gas chromatography with nitrogen-sensitive detection. A special analysis of variance allowed interesting interactions to be distinguished. Results. The steady state was reached after 4 and 6 days for NOCTE and BID respectively; the difference was presumably due to intersubject variability. In accordance with pharmacokinetic theory, the peak-to-trough ratio at steady state was significantly lower (twofold) for BID than for NOCTE. Within BID, a small difference (approx. 10%) was found in the extent of absorption between evening and morning administration. Although statistically significant, this difference meets strict bioequivalence requirements. The regimens NOCTE and BID were found to be bioequivalent for the steady-state area-under-the-curve-curve and the peak time. Bioequivalence testing for the peak level was not meaningful due to the difference in dosing regimens. 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 with previous results. Conclusions. Differences (if any) were found to meet strict bioequivalence requirements and were so small that they are of no clinical consequence. Plenum Publishing Corporation, 1997 Remeron nationallicence mirtazapine nationallicence Org 3770 nationallicence antidepressant nationallicence pharmacokinetics nationallicence Timmer Cees Department of Drug Metabolism & Kinetics, N. V. Organon, P.O. Box 20, 5340 BH, Oss, The Netherlands aut Paanakker Jan Department of Drug Metabolism & Kinetics, N. V. Organon, P.O. Box 20, 5340 BH, Oss, The Netherlands aut Vrijmoed-de Vries Maria Medical Research and Development Unit, N.V. Organon, Oss, The Netherlands aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/1(1997-01-01), 98-102 0724-8741 14:1<98 1997 14 11095 https://doi.org/10.1023/A:1012067703764 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012067703764 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Timmer Cees Department of Drug Metabolism & Kinetics, N. V. Organon, P.O. Box 20, 5340 BH, Oss, The Netherlands aut NATIONALLICENCE 700 1- Paanakker Jan Department of Drug Metabolism & Kinetics, N. V. Organon, P.O. Box 20, 5340 BH, Oss, The Netherlands aut NATIONALLICENCE 700 1- Vrijmoed-de Vries Maria Medical Research and Development Unit, N.V. Organon, Oss, The Netherlands aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/1(1997-01-01), 98-102 0724-8741 14:1<98 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer