Pharmacokinetics of reboxetine in healthy, elderly volunteers

The pharmacokinetic characteristics of reboxetine, a unique selective norad renaline reuptake inhibitor (selective NRI) for the treatment of depression , were studied in 12 healthy, elderly volunteers (mean age 81 years +/- 9 y ears). All subjects received a single 4-mg dose of reboxetine, and plasma r eboxetine concentrations were measured by HPLC. Reboxetine was well tolerated by all subjects. Exposure to reboxetine was h igher in this group of very elderly subjects, compared with data obtained i n a similar study of young, healthy volunteers. C-max in the elderly was 27 1 +/- 86 ng/ml, compared with 111 +/- 28 ng/ml in the young subjects after a single 4-mg dose, although in both groups C-max was observed after 2 h. T he AUC(infinity) was nearly four times that in the younger subjects (8345 /- 3107 ng.h/ml vs. 2106 +/- 881 ng.h/ml) and the t(1/2) was twice as long (24 +/- 6 h vs. 12 +/- 3 h). Renal clearance was also reduced. Reboxetine 8-10 mg/day has been effective and well tolerated in clinical tr ials in non-elderly depressed patients. The increased exposure to reboxetin e observed in our very elderly subjects supports a reduction of the startin g dose to 4 mg/day (in two divided doses) in the elderly.