Absolute bioavailability of reboxetine enantiomers and effect of gender onpharmacokinetics

The absolute bioavailability of reboxetine enantiomers was assessed in six male and six female volunteers. In a two-way crossover study, subjects rece ived 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 d ifferences between treatments for clearance or dose-corrected AUC(0-infinit y) values. The absolute bioavailability was 0.919 and 1.02 for R,R( - ) reb oxetine 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 obs erved, but differences in weight-corrected volumes were not significant. We ight-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 administ ration was 40 and 48% higher in women than men for R,R( - ) reboxetine and S,S( + ) reboxetine, respectively. These results indicate that reboxetine e nantiomers are well absorbed after oral administration and that little firs t-pass metabolism occurs. There are no clinically significant effects of ge nder on the pharmacokinetics of reboxetine enantiomers. Copyright (C) 1999 John Wiley & Sons, Ltd.