Absolute bioavailability of reboxetine enantiomers and effect of gender on pharmacokinetics

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Abstract
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 AUC0–∞ 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. Cmax 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. Copyright © 1999 John Wiley & Sons, Ltd.