生物等效性和生物利用度杂志

抽象的

The Absolute Bioavailability of Desvenlafaxine in Healthy Subjects

Alice I Nichols, Jessica A Behrle, Lyette S Richards, Vernon D Parker, Joel A Posener, Richard Fruncillo and Jeffrey Paul

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.

Methods: 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.

Results 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 intravenous 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%).

Conclusion: Desvenlafaxine has high oral bioavailability and provides an evenly balanced enantiomeric ratio.