Absolute bioavailability of reboxetine enantiomers and effect of gender on pharmacokinetics

✍ Scribed by Joseph C. Fleishaker; Massimiliano Mucci; Cinzia Pellizzoni; Italo Poggesi

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 118 KB
• Volume: 20
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/(sici)1099-081x(199901)20:1<53::aid-bdd157>3.0.co;2-p

✦ Synopsis

The absolute bioavailability of reboxetine enantiomers was assessed in six male and six female volunteers. In a two-way crossover study, subjects received 1.0 mg reboxetine orally and 0.3 mg reboxetine as an intravenous bolus. The R,R(-) and S,S( +) enantiomers in serial plasma and urine samples were determined by a validated LC-MS-MS method. There were no significant differences between treatments for clearance or dose-corrected AUC 0-values. The absolute bioavailability was 0.919 and 1.02 for R,R(-) reboxetine and S,S(+ ) reboxetine, respectively. A secondary objective of the study was to assess gender effects on pharmacokinetics of the enantiomers. Significant differences in volume of distribution between genders were observed, but differences in weight-corrected volumes were not significant. Weight-corrected systemic clearance and oral clearance tended to be lower in males, but this difference reached statistical significance only for weight-corrected oral clearance of R,R(-) reboxetine. C max after oral administration was 40 and 48% higher in women than men for R,R(-) reboxetine and S,S( + ) reboxetine, respectively. These results indicate that reboxetine enantiomers are well absorbed after oral administration and that little first-pass metabolism occurs. There are no clinically significant effects of gender on the pharmacokinetics of reboxetine enantiomers.