Disease relevance of Norvenlafaxine

• Rapid high-performance liquid chromatographic measurement of venlafaxine and O-desmethylvenlafaxine in human plasma. Application to management of acute intoxications [1].

High impact information on Norvenlafaxine

• Concentrations of venlafaxine and O-desmethylvenlafaxine in plasma, urine, and dialysate fluid were determined by high-performance liquid chromatography [2].
• The pharmacokinetics of venlafaxine and its active metabolite O-desmethylvenlafaxine were studied in subjects with various degrees of renal dysfunction, including subjects requiring maintenance hemodialysis [2].
• These results are consistent with previous studies that show CYP2D6 and -3A4 play important roles in the formation of ODV and NDV, respectively [3].
• Studies using expressed cytochromes showed that ODV was formed by CYP2C9, -2C19, and -2D6 [3].
• Formation rates for ODV incubated with human microsomes were consistent with Michaelis-Menten kinetics for a single-enzyme mediated reaction with substrate inhibition [3].

Biological context of Norvenlafaxine

• The biotransformation of venlafaxine (VF) into its two major metabolites, O-desmethylvenlafaxine (ODV) and N-desmethylvenlafaxine (NDV) was studied in vitro with human liver microsomes and with microsomes containing individual human cytochromes from cDNA-transfected human lymphoblastoid cells [3].
• Individuals with ODV/V ratios below 0.3 were all identified as poor metabolizers (PM), with the genotypes *6/*4 (n = 1), *5/*4 (n = 2) or *6/*6 (n = 1) [4].
• AUC of venlafaxine significantly increased by 36% and that of O-desmethylvenlafaxine by 26% ( P<0.01) [5].
• We investigated the relationship between the CYP2D6 polymorphism and steady-state plasma concentration of venlafaxine (VEN) and its primary metabolite o-desmethylvenlafaxine (ODV) in elderly participants receiving venlafaxine-XR for major depression in order to explore the contribution of pharmacogenetics to medication tolerability [6].

Anatomical context of Norvenlafaxine

• The apparent terminal half-lives of desvenlafaxine in plasma, brain and hypothalamus were 3.0, 2.1 and 2.5 h, respectively [7].

Associations of Norvenlafaxine with other chemical compounds

• All antidepressants tested except O-desmethylvenlafaxine showed Pgp inhibitory activity with sertraline, desmethylsertraline, and paroxetine being the most potent, comparable with the well known Pgp inhibitor quinidine [8].
• Pharmacokinetic and pharmacodynamic profiles of the novel serotonin and norepinephrine reuptake inhibitor desvenlafaxine succinate in ovariectomized Sprague-Dawley rats [7].

Analytical, diagnostic and therapeutic context of Norvenlafaxine

• A rapid, accurate, and sensitive high-performance liquid chromatographic (HPLC) method for simultaneous determination of venlafaxine (V) and O-desmethylvenlafaxine (ODV) in plasma and urine has been developed [9].
• A randomized three-period crossover study was conducted to obtain pharmacokinetic and dose proportionality data on the drug and its active metabolite, O-desmethylvenlafaxine [10].
• METHODS: The dose-corrected serum concentrations of venlafaxine and O-desmethylvenlafaxine were analyzed retrospectively in a therapeutic drug-monitoring (TDM) database comprising 94 patients [11].
• AIMS: Interindividual differences in the pharmacokinetics of venlafaxine, a new antidepressant, were shown during early clinical trials in Japan. Venlafaxine is metabolized mainly by CYP2D6 to an active metabolite, O-desmethylvenlafaxine (ODV) [12].
• In a second stage, (+)/(-) enantiomeric ratios for V and ODV were determined using a stereoselective capillary electrophoresis method [13].

References