Psychopharmacology

, Volume 155, Issue 2, pp 148–153

Pharmacokinetics of reboxetine in healthy volunteers with different ethnic descents

  • Pamela E. Hendershot
  • Joseph C. Fleishaker
  • Keh-Ming Lin
  • Inocencia D. Nuccio
  • Russell E. Poland
Original Investigation

DOI: 10.1007/s002130100696

Cite this article as:
Hendershot, P., Fleishaker, J., Lin, KM. et al. Psychopharmacology (2001) 155: 148. doi:10.1007/s002130100696

Abstract

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.

Pharmacokinetics Reboxetine Blacks Asians Ethnicity Race

Copyright information

© Springer-Verlag 2001

Authors and Affiliations

  • Pamela E. Hendershot
    • 1
  • Joseph C. Fleishaker
    • 1
  • Keh-Ming Lin
    • 2
  • Inocencia D. Nuccio
    • 2
  • Russell E. Poland
    • 2
  1. 1.Clinical Pharmacology II, 7215-24-205, Pharmacia and Upjohn, Inc., Kalamazoo, MI 49007USA
  2. 2.Department of Psychiatry, Harbor-UCLA Research and Education Institute, Torrance, CaliforniaUSA
  3. 3.Present address: Thalians Mental Health Center, Los Angeles, CaliforniaUSA