Venlafaxine distribution

Serotonin re-uptake inhibitors are readily absorbed after oral administration and widely distributed throughout the body. Elimination is mainly by hepatic metabolism. Fluoxetine, sertraline and venlafaxine are demethylated to active metabolites. 

In eight patients with major depressive disorder without psychotic features, who did not respond to serotonin reuptake inhibitors therapy when risperidone was added, all improved within 1 week. Furthermore, risperidone also seemed to have beneficial effects on sleep disturbance and sexual dysfunction (272). In an open study in 30 healthy subjects who took risperidone 1 mg orally before and after venlafaxine dosing to steady state, the oral clearance of risperidone fell by 38% and the volume of distribution by 17%, resulting in a 32% increase in AUC renal clearance of 9-hydroxyrisperidone also fell by 20% (273). The authors concluded that these small effects were consistent with the fact that venlafaxine is unlikely to alter the clearance of risperidone, which is mainly by CYP2D6. 

Ilett KE, Hackett LP, Dusci LJ, Roberts MJ, Kristensen JH, Paech M et al. Distribution and excretion of venlafaxine and O-desmethylvenlafaxine in human milk. Br J Clin Pharmacol 1998 45 459-62. 

Venlafaxine is rapidly and well absorbed, but with a bioavailability of 45%, which has been attributed to first-pass metabolism (Table 21.10). Food delays its absorption but does not impair the extent of absorption. Venlafaxine is distributed into breast milk. Venlafaxine is primarily metabolized in the liver by CYP2D6 to its primary metabolite, ODV, which is approximately equivalent in pharmacological activity and potency to... 

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