Effects of age, gender, smoking and co-medication on the pharmacokinetics of venlafaxine and O-desmethylvenlafaxine in everyday clinical practice

Abstract

Venlafaxine (VEN) exerts both serotonin and norepinephrine reuptake inhibition and is widely used as an antidepressant. In a retrospective study, we aimed to examine the influence of age, gender, smoking habits and comedication on the pharmacokinetics of VEN and its main metabolite O-desmethylvenlafaxine (OD-VEN) by therapeutic drug monitoring (TDM). We evaluated all TDM-analyses of VEN during the years 2004–2006 in an unselected sample of patients in the psychiatric university hospitals of Mainz, Regensburg, and Würzburg. To avoid multiple assessments of the same individual only one sample per patient was included. The determination of the serum concentrations of VEN and OD-VEN was performed by a virtually identical HPLC method in the three participating hospitals. Women had higher dose-corrected concentrations than men, and patients over 60 years showed higher concentrations than the younger ones. In smokers lower serum levels were observed than in non-smokers. Comedication with other antidepressants, antipsychotics and mood stabilizers was generally associated with a significantly lowered OD-VEN/VEN ratio. This indicates a delayed metabolism of VEN via CYP2D6, which was observable also in patients receiving a concomitant medication with the known CYP2D6 inhibitor melperone. Altogether our findings confirm that TDM is a useful tool to control pharmacokinetic factors during treatment with VEN and can thus help to avoid inadequate dosage and to recognize drug interactions.