Absolute Bioavailability and Electroencephalographic Effects of Conventional and Extended‐Release Formulations of Venlafaxine in Healthy Subjects
- 8 March 1998
- journal article
- clinical trial
- Published by Wiley in The Journal of Clinical Pharmacology
- Vol. 38 (3), 256-267
- https://doi.org/10.1002/j.1552-4604.1998.tb04423.x
Abstract
Venlafaxine is currently marketed for treatment of depressive disorders as a conventional tablet formulation with a twice or three times daily dosage regimen. The absolute bioavailability of the conventional (CF) and extended‐release (XR) formulations and their effects on electroencephalograms (EEG) and on a visual analog scale (VAS) for nausea were assessed in a randomized, double‐blind, four‐way crossover, placebo‐controlled study of 16 healthy young men who were given either a single 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 1‐week intervals. 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. Regardless of formulation tested, the main EEG changes were an increase in fast beta (20–30 Hz) energy, which was more pronounced over the frontotemporal regions and extended within the full beta range (16–40 Hz). Maximum effect was reached at 6 hours for the CF and reached a plateau from 10 to 24 hours for the XR formulation. A dose‐proportional increase in central activity, expressed as area under the effect curve (AUE) of the beta band, was observed between the CF (50 mg) and XR (75 mg) formulations. Compared with the CF tablet, the XR formulation also produced a much less intense maximum effect and a decrease of 63% in the AUE of nausea normalized by dose. The XR formulation has the same absolute bioavailability and the same central activity as assessed by EEG, but produced less intensive nausea than CF venlafaxine. The present findings suggest that a once‐daily dosage regimen should be sufficient. This was confirmed by several clinical trials in depressive patients.Keywords
This publication has 26 references indexed in Scilit:
- Venlafaxine oxidation in vitro is catalysed by CYP2D6British Journal of Clinical Pharmacology, 1996
- The Pharmacokinetics of Venlafaxine When Given in a Twice-Daily RegimenThe Journal of Clinical Pharmacology, 1995
- Safety and tolerance profile of venlafaxineInternational Clinical Psychopharmacology, 1995
- Pharmacologic profile and efficacy of venlafaxineInternational Clinical Psychopharmacology, 1995
- Clinical utility of venlafaxine in comparison with other antidepressantsInternational Clinical Psychopharmacology, 1995
- VenlafaxineDrugs, 1995
- Metabolic disposition of14C-venlafaxine in mouse, rat, dog, rhesus monkey and manXenobiotica, 1993
- Introduction of a Composite Parameter to the Pharmacokinetics of Venlafaxine and its Active O‐Desmethyl MetaboliteThe Journal of Clinical Pharmacology, 1992
- Biochemical, neurophysiological, and behavioral effects of Wy‐45,233 and other identified metabolites of the antidepressant venlafaxineDrug Development Research, 1991
- AntidepressantsDrugs, 1989