Background and Objective: Desvenlafaxine (administered as desvenlafaxine succinate) is approved for the treatment of major depressive disorder (MDD). If eliminated by the kidney, desvenlafaxine may have more favorable pharmacokinetic or drug-drug interaction profiles compared to its parent compound, venlafaxine, which depends primarily on the CYP2D6 enzyme system. Therefore, the pharmacokinetics and bioavailability of desvenlafaxine was assessed in healthy human subjects.\r\nMethods: In a single-dose, open-label, crossover study, subjects were randomly assigned to 100 mg/d of oral desvenlafaxine or intravenous (50 mg/1 hr) desvenlafaxine. Plasma and urine were collected for 72 hours postdosing and assayed to determine pharmacokinetics and bioavailability of (R)-, (S)-, and (R+S)-desvenlafaxine and N,O-didesmethylvenlafaxine.\r\nResults and Discussion: Pharmacokinetic parameters for (R)- and (S)-desvenlafaxine enantiomers were approximately equivalent for the oral and intravenous formulations of desvenlafaxine. Compared with 50 mg\r\nintravenous desvenlafaxine, 100 mg oral desvenlafaxine had a higher area under the plasma concentration-time curve and an absolute bioavailability of 80.5%. Urinary excretion of total desvenlafaxine and N,O-didesmethylvenlafaxine accounted for 69% of the orally administered desvenlafaxine dose, with the majority of a dose being excreted unchanged or as the glucuronide conjugate (66%).\r\nConclusion: Desvenlafaxine has high oral bioavailability and provides an evenly balanced enantiomeric ratio.
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