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Sex and body weight are major determinants of venlafaxine pharmacokinetics

Schoretsanitis, Georgiosa,i; Haen, Ekkehardb; Hiemke, Christophc; Fay, Biancab; Unholzer, Sandrab; Correll, Christoph U.f,g,h; Gründer, Gerhardd; Paulzen, Michaela,e

International Clinical Psychopharmacology: November 2018 - Volume 33 - Issue 6 - p 322–329
doi: 10.1097/YIC.0000000000000234
ORIGINAL ARTICLES
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We assessed the effect of body weight and BMI on plasma concentrations of venlafaxine (VEN), O-desmethylvenlafaxine (ODVEN), active moiety (AM=VEN+ODVEN), and dose-corrected plasma concentrations (C/D). A database containing concentrations of VEN and ODVEN including 737 of 1594 eligible patients was analyzed. Analyses included sex, body weight, and BMI as well as concentrations of VEN, ODVEN, AM, and C/D. A positive correlation was detected between body weight and daily dosage (rs=0.168, P<0.001). A negative correlation was found between body weight and AM (rs=−0.124, P=0.001) and ODVEN (rs=−0.137, P<0.001). Negative correlations were also found between body weight and C/D ratios (C/D VEN: rs=−0.134, P<0.001, C/D ODVEN: rs=−0.239, P<0.001, C/D AM: rs=−0.256, P<0.001). No correlations were detected between BMI and concentrations for VEN, ODVEN, and AM. Comparing low-BMI (<20 kg/m²), medium-BMI (20–29.9 kg/m²), and high-BMI (≥30 kg/m²) groups, higher values of some pharmacokinetic variables in the lower BMI group did not remain significant after controlling for sex. Women had higher VEN, ODVEN, AM, and C/D values for AM, VEN, and ODVEN than men (P<0.001 for all comparisons). Our results highlight the role of different pharmacokinetically relevant parameters and foremost of sex as mediators for the effect of BMI on VEN metabolism.

aDepartment of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, JARA – Translational Brain Medicine

bDepartment of Psychiatry and Psychotherapy and Department of Pharmacology and Toxicology, University of Regensburg, Regensburg

cDepartment of Psychiatry and Psychotherapy and Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of Mainz, Mainz

dDepartment of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim

eAlexianer Hospital Aachen, Aachen, Germany

fThe Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen Oaks

gHofstra Northwell School of Medicine, Hempstead

hThe Feinstein Institute for Medical Research, Manhasset, New York, USA

iUniversity Hospital of Psychiatry, Bern, Switzerland

Correspondence to Georgios Schoretsanitis, MD, Department of Psychiatry, Psychotherapy and Psychosomatics, and JARA – Translational Brain Medicine, RWTH Aachen University, Pauwelsstr. 30, 52074 Aachen, Germany Tel: +49 241 808 9508; fax: +49 241 808 2401; e-mail: george.schor@gmail.com

Received April 13, 2018

Accepted June 5, 2018

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