Hemodynamic effects of reboxetine in healthy male volunteers

Background: Reboxetine [(R,S)-2[(R,S)-alpha-(2-ethoxyphenoxy)benzyl]morphol ine methanesulfonate] is a racemic compound that consists of equal proporti ons of R,R- and S,S-enantiomers. This study investigated the hemodynamic ef fects of reboxetine and the R,R-enantiomer compared with placebo in volunte ers, The pharmacokinetics of reboxetine and its enantiomers were also inves tigated in the study. Methods: Nine healthy, male volunteers received single doses of 4 mg reboxe tine, 2 mg R,R-enantiomer, and placebo at weekly intervals. Reboxetine and the R,R-enantiomer were well tolerated in all volunteers, Results: The heart rates of patients in the supine and standing positions w ere increased after reboxetine administration compared with the R,R-enantio mer (P < .05, except supine heart rate at 6 hours) and placebo (P < .05), S upine systolic and diastolic blood pressure was also increased by 3 +/- 4 a nd 1 +/- 4 mm Hg respectively, after reboxetine compared with R,R-enantiome r (-2 +/- 4 and 4 +/- 3 mm Hg) and placebo (-4 +/- 4 and -4 +/- 4 mm Hg) ad ministration. The systolic and diastolic blood pressure measurements for su bjects while standing did not differ significantly among treatments. There was no significant difference between the maximum plasma concentration, mea n time to maximum plasma concentration, plasma half-life, or area under the plasma concentration-time curve (AUC) of the R,R-enantiomer after reboxeti ne or R,R enantiomer administration. The ratio of the mean AUC values for t he R,R- and S,S-enantiomers was 2,1, Conclusion: These findings suggest that the S,S-enantiomer is responsible f or the hemodynamic effects of reboxetine in humans. Increases in supine blo od pressure after reboxetine administration may be interpreted as regressio n to the mean value and not caused by any treatment effect.