Mirtazapine oral single dose kinetics in patients with different degrees of renal failure

✍ Scribed by F. Bengtsson; P. Höglund; C. Timmer; J. Hegbrant

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 152 KB
• Volume: 13
• Category: Article
• ISSN: 0885-6222
• DOI: 10.1002/(sici)1099-1077(199807)13:5<357::aid-hup8>3.0.co;2-k

✦ Synopsis

To investigate pharmacokinetic parameters, as well as safety of mirtazapine in patients with renal failure, an openlabelled, single oral dose study was performed in normal healthy controls and in patients with mild, moderate and severe renal failure, as distinguished by glomerular ®ltration 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 concentration of this racemic compound was increased in patients with moderate (GFR 22+6 ml/min) and severe (GFR 2+5 ml/min) renal failure compared to controls. The AUCs were, however, unaected by mild renal failure (GFRs 61+14 ml/min). The oral clearance was found to be lower in patients with moderate or severe renal failure, as well as in females compared to males irrespective of degree of renal failure. The magnitude of renal failure was found not to in¯uence the elimination 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 morning 15 mg/day dose of mirtazapine was well tolerated by patients with renal 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 optimize 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 currently under development for mirtazapine.