Pharmacokinetics of reboxetine in elderly patients with depressive disorders

<(Objectives)under bar>: To examine the pharmacokinetic characteristics of the selective norepinephrine reuptake inhibitor, reboxetine, in elderly pat ients with depression. <(Patients)under bar>: Twelve female inpatients (mea n age 80 +/- 4 years) with major depressive or dysthymic disorder were enro lled in a 4-week uncontrolled study of oral reboxetine 2 - 8 mg/day. <(Meth ods)under bar>: After a one-week washout period, patients were randomized i nto two groups (groups A and B, n = 6/group). Reboxetine was given twice da ily, starting with 2 mg/day during week 1 and increasing by 2 mg/day each w eek 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 pharmac okinetics. <(Results)under bar>: Reboxetine displayed linear pharmacokineti cs, with dose-proportional changes, in elderly depressed patients. Mean tot al urinary recovery ranged from 4.06 to 6.17%. The mean area under the plas ma concentration-time curve (AUC(tau)) and the maximum plasma drug concentr ation (C-max) showed considerable variation between patients; at a dosage o f 4 mg/day, AUC(tau) was 1466 - 6866 ng x h/ml and C-max ranged from 169 to 663 ng/ml. <(Conclusions)under bar>: The pharmacokinetics of reboxetine ar e linear across the dosage range of 2 - 8 mg/day in elderly depressed patie nts, although C-max and AUC(tau) 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.