Pharmacokinetics of reboxetine in healthy volunteers with different ethnic descents

• Published in: Psychopharmacologia 2001-05, Vol.155 (2), p.148-153
• Main Authors: HENDERSHOT, Pamela E, FLEISHAKER, Joseph C, LIN, Keh-Ming, NUCCIO, Inocencia D, POLAND, Russell E
• Format: Article
• Language: English
• Subjects: Adrenergic Uptake Inhibitors - blood; Adrenergic Uptake Inhibitors - pharmacokinetics; Adult; African Continental Ancestry Group; Area Under Curve; Asian Continental Ancestry Group; Biological and medical sciences; Blood Proteins - metabolism; Continental Population Groups; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System - metabolism; Dialysis; Enantiomers; Equilibrium dialysis; European Continental Ancestry Group; Female; Humans; Male; Medical sciences; Middle Aged; Minority & ethnic groups; Mixed Function Oxygenases - metabolism; Morpholines - blood; Morpholines - pharmacokinetics; Neuropharmacology; Pharmacodynamics; Pharmacokinetics; Pharmacology. Drug treatments; Protein Binding; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Reboxetine; Sample Size; White people
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s002130100696

Ethnicity can affect the pharmacokinetics and pharmacodynamics of psychopharmacologic drugs. Reboxetine disposition differences among Asians, blacks, and Caucasians were examined. Healthy subjects (12 Asians, 12 blacks, 12 Caucasians) received a single oral dose of one 4-mg reboxetine tablet in an open label, parallel study design. Plasma concentrations of reboxetine enantiomers [R,R(-) reboxetine and predominantly active S,S(+) reboxetine] were quantified using HPLC-MS-MS. Plasma unbound fractions of reboxetine enantiomers were evaluated by equilibrium dialysis. Ethnic group effects on pharmacokinetic parameters were assessed by ANOVA. Mean S,S(+) reboxetine CLPO for blacks was significantly greater, compared to Asians and Caucasians (154+/-82 ml/min, 101+/-19 ml/min and 101+/-18 ml/min, respectively). Mean S,S(+) reboxetine free fractions (fu) were significantly greater for Asians and blacks, compared to Caucasians (3.04+/-1.28%, 2.89+/-0.69%, and 1.99+/-0.58%, respectively). S,S(+) Reboxetine unbound clearance (CLu) was significantly less for Asians, compared to blacks and Caucasians (3742+/-1468 ml/min, 5187+/-2027 ml/min, and 5294+/-1163 ml/min, respectively). S,S(+) Reboxetine mean unbound AUC (AUCu) in these groups were 20.2+/-7.1 ng.h/ml, 14.6+/-5.1 ng.h/ml, and 13.2+/-3.2 ng.h/ml, respectively. AUCu was significantly greater for Asians. CLu and AUCu did not differ significantly between blacks and Caucasians. Ethnic effects of R,R(-) reboxetine were similar to those observed for S,S(+) reboxetine. The AUCu difference between Asian and black and Caucasian subjects was modest. Tolerability differences among groups were not observed. No dosage adjustment is necessary for Asians or blacks.