Pharmacokinetics of reboxetine in healthy volunteers with different ethnic descents
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- Hendershot, P., Fleishaker, J., Lin, KM. et al. Psychopharmacology (2001) 155: 148. doi:10.1007/s002130100696
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Rationale: Ethnicity can affect the pharmacokinetics and pharmacodynamics of psychopharmacologic drugs. Objectives: Reboxetine disposition differences among Asians, blacks, and Caucasians were examined. Methods: 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. Results: 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. Conclusions: 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.