Venlafaxine pharmacokinetics focused on drug metabolism and potential biomarkers

Venlafaxine (VEN) is one of the safest and most effective drugs used in the treatment of selective serotonin reuptake inhibitors-resistant depression, and thereby it is nowadays one of the most commonly prescribed antidepressants. Nevertheless, patients treated with antidepressant drugs including VEN have exhibited large inter-individual variability in drug outcomes, possibly due to the influence of genetic and nongenetic factors on the drug pharmacokinetics and/or pharmacodynamics. Among them, an increased interest has emerged over the last few years on the genetic and/or phenotypic profile for drug-metabolizing cytochrome P450 isoenzymes and drug transporters such as potential predictive pharmacokinetic-based biomarkers of the variability found in drug biodisposition and antidepressant response. The integration of some of these key therapeutic biomarkers with classic therapeutic drug monitoring constitutes a promising way to individualization of VEN's pharmacotherapy, offering to clinicians the ability to better predict and manage pharmacological treatments to maximize the drug effectiveness. Thus, this review provides an extensive discussion of the pharmacokinetics of VEN focusing in particular on metabolism issues, without forgetting the clinically relevant sources of pharmacokinetics variability (mainly the genetic sources) and aiming on the identification of phenotypic and/or genetic biomarkers for therapy optimization.