Pharmacokinetics of reboxetine in elderly patients with depressive disorders
Poggesi, I.; Pellizzoni, C.; Fleishaker, J.C.
International Journal of Clinical Pharmacology and Therapeutics 38(5): 254-259
2000
ISSN/ISBN: 0946-1965 PMID: 10839469 Document Number: 512456
Objectives: To examine the pharmacokinetic characteristics of the selective norepinephrine reuptake inhibitor, reboxetine, in elderly patients with depression. Patients: Twelve female inpatients (mean age 80 +- 4 years) with major depressive or dysthymic disorder were enrolled in a 4-week uncontrolled study of oral reboxetine 2 - 8 mg/day. Methods: After a one-week washout period, patients were randomized into two groups (groups A and B, n = 6/group). Reboxetine was given twice daily, starting with 2 mg/day during week 1 and increasing by 2 mg/day each week to 8 mg/day in week 4. Pharmacokinetic evaluations were carried out at two dosage levels in each group: at the end of weeks 1 and 3 in group A (2 and 6 mg/day), and at the end of weeks 2 and 4 in group B (4 and 8 mg/day). Blood and urine samples were taken for determination of reboxetine pharmacokinetics. Results: Reboxetine displayed linear pharmacokinetics, with dose-proportional changes, in elderly depressed patients. Mean total urinary recovery ranged from 4.06 to 6.17%. The mean area under the plasma concentration-time curve (AUCtau) and the maximum plasma drug concentration (Cmax) showed considerable variation between patients; at a dosage of 4 mg/day, AUCtau was 1466-6866 ngXh/ml and Cmax ranged from 169 to 663 ng/ml. Conclusions: The pharmacokinetics of reboxetine are linear across the dosage range of 2 - 8 mg/day in elderly depressed patients, although Cmax and AUCtau values are higher (and more variable) than in young adults. These results support the use of a lower starting dose (4 mg/day) of reboxetine in the elderly.