REVIEW OF THE PHARMACOKINETICS AND METABOLISM OF REBOXETINE, A SELECTIVE NORADRENALINE REUPTAKE INHIBITOR

The pharmacokinetics and metabolism of reboxetine, a selective noradre naline reuptake inhibitor, in humans and animal models are reviewed he re. Reboxetine has potent antidepressant activity, low affinity for al pha-adrenergic and muscarinic receptors and low toxicity in animals. I t is a mixture of (R,R) and (S,S) enantiomer, the latter being more po tent but no qualitative differences in pharmacodynamic properties are observed between the two. Humans rapidly absorb reboxetine (t(max) abo ut 2 h) with a terminal half-life of elimination (t(1/2)) of 13 h, all owing twice-daily administration. Animal models also rapidly absorb re boxetine (t(max) 0.5-2 h) but t(1/2) was 1-2 h. Food does not affect b ioavailability. There were no major inter-species differences in the m etabolic profile of reboxetine. Elimination is principally renal in hu mans and monkeys. Reboxetine has linear pharmacokinetics in young, hea lthy males for single doses of 1-5 mg and in elderly, female depressed patients (up to 4 mg b.i.d.). Multiple dosing, gender or liver insuff iciency had no significant effects on the pharmacokinetics. Elderly (p articularly frail elderly) patients and patients with severe renal imp airment may need dose reduction. Reboxetine shows no clinically releva nt interaction with lorazepam and has no inhibitory effects on the maj or enzymes involved in drug metabolism. It may be possible to use rebo xetine in combination with monoamine oxidase inhibitors as it has no i nhibitory effect on this enzyme; in addition, it may protect patients against tyramine-induced reactions. In conclusion, reboxetine seems to be an antidepressant with negligible interference with the pharmacoki netics of other drugs thus fewer drug-drug interactions are expected. (C) 1997 Elsevier Science B.V.