The Absolute Bioavailability of Desvenlafaxine in Healthy Subjects
- *Corresponding Author:
- Alice I. Nichols
Pfizer Inc, formerly Wyeth Research
500 Arcola Rd, Collegeville
PA 19426, USA
Fax: 484-865- 9075
E-mail: [email protected]
Received Date: January 26, 2012; Accepted Date: February 22, 2012; Published Date: February 24, 2012
Citation: Nichols AI, Behrle JA, Richards LS, Parker VD, Posener JA, et al. (2012) The Absolute Bioavailability of Desvenlafaxine in Healthy Subjects. J Bioequiv Availab 4: 018-023. doi: 10.4172/jbb.1000105
Copyright: © 2012 Nichols AI, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.