Dose proportionality of reboxetine enantiomers in healthy male volunteers

Reboxetine is a racemic mixture of FCE 22071 and FCE 21684 enantiomers. The pharmacokinetics of the enantiomers of reboxetine were observed to be line ar in male healthy subjects (n = 6) after the administration of 1.5, 3, 4.5 mg dose of reboxetine as solutions. Kinetic analysis was based on chiral H PLC assay of the enantiomers in plasma collected up to 72 h after each admi nistration. C-max and AUC were more than double for FCE 22071 (C-max: 38.3 +/- 13.5, 76.6 +/- 26.3, 99.8 +/- 24.1 ng/mL and AUC(infinity): 605.8 +/- 2 33.2, 1288.3 +/- 796.4, 1780.7 +/- 669.3 ng.h/ml for 1.5, 3, 4.5 mg, respec tively) than for FCE 21684 (C-max: 15.2 +/- 5.3, 34.6 +/- 14.0, 43.1 +/- 12 .3 ng/mL and AUC(infinity): 247.0 +/- 103.9, 529.1 +/- 278.4, 773.0 +/- 355 .3 ng.h/ml), whatever the administered dose. The half-lives of the enantiom ers were similar (FCE 22071: 13.1, 11.0, 12.6 h and FCE 21684: 12.8, 11.2, 12.2 h after 1.5, 3, 4.5 mg, respectively) and not substantially affected b y the dose level. (C) 1999 John Wiley & Sons, Ltd.