An open‐label, randomized, crossover study of the relative bioavailability of desvenlafaxine after oral administration of extended‐release venlafaxine and sustained‐release desvenlafaxine succinate in healthy subjects

Background/Aims To assess the relative bioavailability of desvenlafaxine (DV) after single oral doses of extended-release venlafaxine (VEN-ER) and sustained-release desvenlafaxine succinate (DVS-SR) in healthy subjects. Methods A randomized single-dose crossover study was conducted with 35 healthy male and female subjects. The 4 oral doses were 75 and 150 mg of VEN-ER and 75 and 150 mg of DVS-SR given after a medium-fat breakfast. Routine laboratory tests, vital signs, and electrocardiograms (ECG) were measured throughout the study. A 100-mm Visual Analog Scale (VAS) for nausea was used to evaluate the profile for nausea during treatment periods. The maximum nausea experienced (Emax) was calculated. Plasma concentrations of venlafaxine (VEN) and DV were analyzed by model-independent methods. Results DV was well absorbed with higher values for Cmax and AUC after administration of DVS-SR in comparison with VEN-ER. There was a statistically significant difference in nausea intensity between DVS-SR and VEN-ER. Mean VAS Emax values for DVS-SR were approximately 6-fold lower for the 75 mg doses and 2-fold lower for the 150 mg doses compared with the same doses of VEN-ER. Conclusion DVS-SR provided good absorption and drug availability to the systemic circulation with DV plasma concentrations higher than those obtained after similar doses of VEN-ER. Nausea was less severe with DVS-SR than with VEN-ER. Clinical Pharmacology & Therapeutics (2005) 77, P86–P86; doi: 10.1016/j.clpt.2004.12.222