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 linear 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 HPLC assay of the enantiomers in plasma collected up to 72 h after each administration. 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+/-233.2, 1288. 3+/-796.4, 1780.7+/-669.3 ng. h/mL for 1.5, 3, 4.5 mg, respectively) 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 enantiomers 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 by the dose level.
Rey
E
E
Clinical Pharmacology, Hôpital Saint-Vincent de Paul, Paris, France.
Dostert
P
P
d'Athis
P
P
Jannuzzo
M G
MG
Poggesi
I
I
Olive
G
G
D000284:Administration, Oral; D018759:Adrenergic Uptake Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016014:Linear Models; D008297:Male; D009025:Morpholines / Q000097:blood / Q000493:pharmacokinetics*; D000077593:Reboxetine; D013237:Stereoisomerism
D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D009025:Morpholines; D000077593:Reboxetine