Venlafaxine pharmacokinetics focused on drug metabolism and potential biomarkers

Abstract

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.

Determination of antidepressants in human urine extracted by magnetic multiwalled carbon nanotube poly(styrene‐co‐divinylbenzene) composites and separation by capillary electrophoresis

“…Among these drugs, the selective serotonin reuptake inhibitors (SSRIs) are the most significant class of antidepressants marketed in recent years, even though considering the occurrence of adverse effects associated to their consumption . Among the SSRIs, fluoxetine, citalopram, and sertraline are some of the most prescribed active principles . Furthermore, newer atypical antidepressants including target other neurotransmitters either alone or in addition to serotonin, such as venlafaxine, are currently administered and commonly prescribed worldwide .…”

Recent advances in liquid chromatographic methods for the determination of selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors

“…It should be noted that desvenlafaxine has little or no induction or inhibition of various CYP enzymes and its metabolism is only minimally mediated by these enzymes. The average T max , average T 1/2 , log P , and p K a values of venlafaxine are 2 h, 5 h, 2.9 and 10, respectively; the average T max , average T 1/2 , log P , and p K a values of desvenlafaxine are 7 h, 11 h, 2.6 and 9.4, respectively (Holliday & Benfield, ; Magalhães, Alves, Llerena, & Falcão, ).…”

Simultaneous Determination of Methadone, Fluoxetine, Venlafaxine and Their Metabolites in Rat Plasma by UPLC–MS/MS for Drug Interaction Study

“…Methadone is mainly metabolized by hepatic enzymes into 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium (EDDP), involving CYP3A4, 2C9 and 2D6 [3] and considered as a potent CYP2C19 enzyme inhibitor [4]. As an antidepressant, venlafaxine (VEN) is of the serotonin-norepinephrine reuptake inhibitor (SNRI) class and thereby is nowadays one of the most commonly prescribed antidepressants [5]. Venlafaxine is mainly transformed into O-desmethylvenlafaxine (ODV) in vivo [6].…”