Precision dosing of venlafaxine during pregnancy: a pharmacokinetics modelling approach

Abstract

Abstract Objectives Venlafaxine exposure through gestation is affected by the longitudinal changes in maternal physiology. Confounding treatment is also the impact of CYP2D6 polymorphisms affecting plasma concentrations of venlafaxine. Methods A pharmacokinetic modelling approach was employed to assess variations in maternal and foetal cord venlafaxine levels throughout gestation and to identify appropriate doses to maintain venlafaxine levels within the therapeutic range. Key findings Throughout gestation, there was a significant decrease in simulated venlafaxine trough plasma concentrations in both extensive metaboliser (EM) and ultra-rapid metaboliser (UM) phenotypes. Approximately 70%–87% of EM and UM phenotypes exhibited trough venlafaxine plasma concentrations below the therapeutic level (<25 ng/ml), which increased to 96% at week 30. While for poor metabolizer (PM) phenotypes, the percentage was approximately 4%. Conclusion The standard daily dose of 75 mg required adjustment for all phenotypes examined during gestation. A daily dose of 37.5–112.5 mg is appropriate for PM throughout pregnancy. For EM, a dose of 225 mg daily in the first trimester, 262.5 mg daily in the second trimester, and 375 mg daily in the third trimester is suggested to be optimal. For UM, a dose of 375 mg daily throughout gestation is suggested to be optimal.