Pharmacokinetics of reboxetine in healthy, elderly volunteers

Abstract

The pharmacokinetic characteristics of reboxetine, a unique selective noradrenaline reuptake inhibitor (selective NRI) for the treatment of depression, were studied in 12 healthy, elderly volunteers (mean age 81 years +/- 9 years). All subjects received a single 4-mg dose of reboxetine, and plasma reboxetine concentrations were measured by HPLC. Reboxetine was well tolerated by all subjects. Exposure to reboxetine was higher in this group of very elderly subjects, compared with data obtained in a similar study of young, healthy volunteers. Cmax in the elderly was 271 +/- 86 ng/ml, compared with 111 +/- 28 ng/ml in the young subjects after a single 4-mg dose, although in both groups Cmax was observed after 2 h. The AUC infinity was nearly four times that in the younger subjects (8345 +/- 3107 ng.h/ml vs. 2106 +/- 881 ng.h/ml) and the t1/2 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 trials in non-elderly depressed patients. The increased exposure to reboxetine observed in our very elderly subjects supports a reduction of the starting dose to 4 mg/day (in two divided doses) in the elderly.

Effects of Age and Sex on the Pharmacokinetics, Safety, and Tolerability of Oral Desvenlafaxine in Healthy Adults

“…A significant decrease in clearance with increasing age was also observed in a population pharmacokinetic analysis of duloxetine [27], and in an analysis of therapeutic drug monitoring samples for citalopram [23]. In general, these differences have been attributed to age-related decline in hepatic or renal function [27,[31][32][33][34]. In the current study, age-related differences may in large part be due to declining renal function.…”

The Impact of the Selective Monoamine Reuptake Inhibitors Reboxetine and Citalopram on Visually-Evoked Event-Related Potentials in Depressed Patients

“…At 8 : 05 a. m. the patients randomized in the citalopram group received 20 mg of citalopram (Cipramil , Lundbeck) as a single oral dose and at 12 : 00 a. m. blood samples for cortisol and prolactin measurements were drawn. We chose different time points for the second blood sampling because after oral reboxetine or citalopram challenge, the highest reboxetine level in plasma can be expected two hours later [3] and the highest citalopram level in plasma can be expected from two to four hours later [25,27].…”

Pharmacological treatment of depression in older people

“…Recent evidence suggests that reboxetine is effective in older people with depression but causes less hypotension and fewer serious side-effects than TCAs (Katona et al, 1999). However, renal clearance is reduced in older patients (Bergmann et al, 2000). The pharmacokinetics of reboxetine are linear following both single and multiple oral doses and the plasma halflife is approximately 12 hours.…”

“…The drug was well tolerated although nausea (11.9%) and headache (10%) were relatively common (Aguglia, 2000). However, because of these side-effects some authors have recommended that older patients should be started on 4mg/day in two divided doses (Bergmann et al, 2000). Controlled trials in older people are still needed.…”