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The absolute bioavailability of an oral sustained‐release formulation of desvenlafaxine succinate in healthy subjects
Author(s) -
Parker V. D.,
Richards L. S.,
Nichols A. I.,
Behrle J. A.,
Fruncillo R. J.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.12.071
Subject(s) - bioavailability , pharmacokinetics , cmax , crossover study , pharmacology , chemistry , oral administration , enantiomer , chromatography , medicine , stereochemistry , alternative medicine , pathology , placebo
Background/Aims To assess the absolute bioavailability of sustained‐release desvenlafaxine succinate (DVS‐SR) and pharmacokinetics of desvenlafaxine (DV) in healthy subjects. Methods In this single‐dose, open‐label, 2‐period crossover study, subjects were randomized to receive either a 1× 100‐mg oral tablet of DVS‐SR or a single 50 mg/1 hr intravenous (IV) infusion of desvenlafaxine succinate (DVS) in each period. Plasma was assayed for the total racemic mixture (R+S) and ratio (R/S) of DV. The absolute bioavailability was calculated from oral and IV AUC values of the racemic mixture of DV. Results A total of 14 subjects were enrolled and completed the study. DVS‐SR was generally well tolerated. There were no clinically important changes in routine laboratory tests, vital signs measurements, and electrocardiograms (ECG). The 50‐mg IV formulation had a higher C max (232 ng/mL) than the 100‐mg oral formulation (160 ng/mL). The half‐lives were similar, ranging from 14 to 15 hours, and the 100‐mg oral formulation of DVS‐SR had a higher overall exposure (AUC oral 3996 vs AUC IV 2443 ng*h/mL). The absolute bioavailability of the oral formulation was 80.5%. The concentration profiles for R and S enantiomers were approximately equivalent to each other for both the IV and oral formulations. Conclusion DVS‐SR provided good oral bioavailability (80.5%) and an evenly balanced enantiomeric ratio. Clinical Pharmacology & Therapeutics (2005) 77 , P47–P47; doi: 10.1016/j.clpt.2004.12.071