Pharmacokinetics of single-dose reboxetine in volunteers with renal insufficiency

Reboxetine is a new selective norepinephrine reuptake inhibitor (selective NRI) for the short- and long-term treatment of depression that is effective and well tolerated at a dose of 8 to 10 mg/day. This study assessed the ph armacokinetics of reboxetine in volunteers with renal impairment. A single 4 mg dose of reboxetine was administered to a fetal of 18 volunteers with m ild (n = 6), moderate (n = 6), orsevere (n = 6) renal impairment (creatinin e clearance: 56-64, 26-51, and 9-19 ml/min, respectively), and reboxetine c oncentrations were measured in plasma by HPLC. Mean AUC(infinity) increased by 43% (mild vs. severe; p < 0.01) as renal function declined, while renal clearance and total urinary excretion of unchanged reboxetine decreased by 67% and 62%, respectively (mild vs. severe; p < 0.01 for both parameters), t(max) and t(1/2) were not significantly different between groups, In comp arison with historical data from young healthy volunteers, AUC(infinity)and t(1/2) are at least doubled in volunteers with renal impairment, while CLx is halved. This pharmacokinetic study has shown that increasing renal dysf unction leads to increasing systemic exposure to reboxetine, particularly i n severe renal insufficiency, although reboxetine was well tolerated by all volunteers. Thus, a reduction of the starting dose of reboxetine to 2 mg t wice daily would be prudent in patients with renal dysfunction. (C) 2000 th e American College of Clinical Pharmacology.