MIRTAZAPINE ORAL SINGLE-DOSE KINETICS IN PATIENTS WITH DIFFERENT DEGREES OF RENAL-FAILURE

To investigate pharmacokinetic parameters, as well as safety of mirtaz apine in patients with renal failure, an open-labelled, single oral do se study was performed in normal healthy controls and in patients with mild, moderate and severe renal failure, as distinguished by glomerul ar filtration rates (GRFs) of Cr-EDTA (values corrected per 1.73 m(2) body surface area). Each group comprised of 10 volunteers (5 males and 5 females). The results show that after a single oral morning dose of 15 mg of mirtazapine, the area under the curve (AUC) for the plasma c oncentration of this racemic compound was increased in patients with m oderate (GFR 22 +/- 6 ml/min) and severe (GFR 2 +/- 5 ml/min) renal fa ilure compared to controls. The AUCs were, however, unaffected by mild renal failure (GFRs 61 +/- 14 mi/min). The oral clearance was found t o be lower in patients with moderate or severe renal failure, as well as in females compared to males irrespective of degree of renal failur e. The magnitude of renal failure was found not to influence the elimi nation half-life of mirtazapine (overall mean +/- SD = 36.3 +/- 8.1 h) . The adverse experiences (AEs) were reported with similar incidences in all groups, and described as being mild or moderate in nature. The most commonly reported AEs were somnolence and tiredness occurring in one half and one third of the subjects, respectively. The single morni ng 15 mg/day dose of mirtazapine was well tolerated by patients with r enal failure, irrespective of degree of severity. Further research is needed to evaluate repeated dose pharmacokinetics and tolerability of mirtazapine in patients with renal failure. An additional option to op timize treatment of an individual, medically compromised patient is to apply Therapeutic Drug Monitoring (TDM) routines for dose adjustments . Such a pharmacokinetic postmarketing surveillance program is current ly under development for mirtazapine. (C) 1998 John Wiley & Sons, Ltd.