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 pharmacokinetics of reboxetine in volunteers with renal impairment. A single 4 mg dose of reboxetine was administered to a total of 18 volunteers with mild (n = 6), moderate (n = 6), or severe (n = 6) renal impairment (creatinine clearance: 56-64, 26-51, and 9-19 ml/min, respectively), and reboxetine concentrations 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). tmax and t1/2 were not significantly different between groups. In comparison with historical data from young healthy volunteers, AUC infinity and t1/2 are at least doubled in volunteers with renal impairment, while CLr is halved. This pharmacokinetic study has shown that increasing renal dysfunction leads to increasing systemic exposure to reboxetine, particularly in severe renal insufficiency, although reboxetine was well tolerated by all volunteers. Thus, a reduction of the starting dose of reboxetine to 2 mg twice daily would be prudent in patients with renal dysfunction.
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.
The study objective was to compare the bioavailability of codeine and ibuprofen after oral administration of the two drugs alone or in association. The study was performed in three different periods, each separated by a wash-out of 6 days. Plasma concentrations were measured in 24 healthy volunteers after administration of a single oral dose of codeine phosphate (25 mg) and/or ibuprofen (200 mg). Codeine and ibuprofen assays were performed using two different HPLC methods. The relative bioavailabilities of codeine and ibuprofen (alone or in association) were 106 +/- 24% (mean +/- sd) and 101 +/- 19%, respectively. The results obtained demonstrated that bioavailabilities of codeine and ibuprofen were not modified when the two drugs were administrated alone or in association.
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