An open-label, randomized, single-dose, dose-proportionality study of oral doses of a sustained-release formulation of desvenlafaxine succinate in healthy subjects

Abstract

Background/Aims To assess the dose-proportionality of single oral doses of a sustained-release formulation of desvenlafaxine succinate (DVS-SR) in healthy subjects. Methods A randomized single-dose crossover study was conducted in 24 healthy male subjects. Three (3) doses (100, 300, and 600 mg) were given by using 100-mg tablets after a medium-fat breakfast. Routine laboratory tests, vital signs, and electrocardiograms (ECG) were measured throughout the study. Plasma concentrations of desvenlafaxine (DV) were analyzed by model-independent methods and linear dose proportionality of Cmax and AUC were assessed by an exponential regression model. Results DV was slowly absorbed (mean tmax of 7 to 8 hours) with slow elimination (mean t1/2 of 11 hours). Cmax and AUC increased linearly over the dose range of 100 to 600 mg. The between-subject variability was low with the percent coefficient of variations (%CV) under 25% for Cmax, t1/2, and AUC. Nausea and dizziness were the most common adverse events. No clinically relevant changes occurred in ECG intervals and laboratory tests. Conclusion Increases in the Cmax and AUC of DV were linear over the dose range studied (100, 300, and 600 mg). DVS-SR was generally well tolerated at all doses. Clinical Pharmacology & Therapeutics (2005) 77, P82–P82; doi: 10.1016/j.clpt.2004.12.207