ABSOLUTE BIOAVAILABILITY AND ELECTROENCEPHALOGRAPHIC EFFECTS OF CONVENTIONAL AND EXTENDED-RELEASE FORMULATIONS OF VENLAFAXINE IN HEALTHY-SUBJECTS

Venlafaxine is currently marketed for treatment of depressive disorder s as a conventional tablet formulation with a twice or three times dai ly dosage regimen. The absolute bioavailability of the conventional (C F) and extended-release (XR) formulations and their effects on electro encephalograms (EEG) and on a visual analog scale (VAS) for nausea wer e assessed in a randomized, double-blind, four-way crossover, placebo- controlled study of Is healthy young men who were given either a singl e oral dose of 50 mg of CF venlafaxine, 75 mg of XR venlafaxine, or an intravenous dose of 10 mg of venlafaxine, or a placebo at I-week inte rvals. The absolute bioavailability of venlafaxine was between 40% and 45% and was similar for both the CF and XR formulations. Venlafaxine produced central effects of a desipramine-like antidepressant. Regardl ess of formulation tested, the main EEG changes were an increase in fa st beta (20-30 Hz) energy, which was more pronounced over the frontote mporal regions and extended within the full beta range (26-40 Hz). Max imum effect was reached at 6 hours for the CF and reached a plateau fr om 10 to 24 hours for the XR formulation. A dose-proportional increase in central activity, expressed as area under the effect curve (AUE) o f the beta band, was observed between the CF (50 mg) and XR (75 mg) fo rmulations. Compared with the CF tablet, the XR formulation also produ ced a much less intense maximum effect and a decrease of 63 % in the A UE of nausea normalized by dose. The XR formulation has the same absol ute bioavailability and the same central activity as assessed by EEG, but produced less intensive nausea than CF venlafaxine. The present fi ndings suggest that a once-daily dosage regimen should be sufficient. This was confirmed by several clinical trials in depressive patients.