PHARMACOKINETICS AND EFFECT OF FOOD ON THE BIOAVAILABILITY OF ORALLY-ADMINISTERED VENLAFAXINE

Venlafaxine is a unique antidepressant currently under evaluation for treatment of various affective disorders. The pharmacokinetics and rel ative bioavailability of venlafaxine were evaluated in healthy volunte ers after oral administration. The bioavailability of 50 mg of venlafa xine as a tablet relative to a solution was determined in a two-period randomized crossover study. The rate of absorption from the gastroint estinal tract was assessed by the time to peak plasma concentration (t (max)) a model-dependent calculation of the first-order absorption rat e constant, and a model-independent calculation of mean residence time . The extent of absorption was assessed by peak plasma concentration ( C-max) and area under the concentration-time curve (AUC). No statistic ally significant differences were observed between the two formulation s for either the rate or extent of absorption. Similarly, systemic con centrations of the active O-demethylated metabolite did not significan tly differ after administration of the two venlafaxine formulations. A UC ratios indicated that the relative bioavailabilities of the parent drug, and formulation of metabolite were approximately 98% and 92%, re spectively, for the tablet versus the solution. A separate study was c onducted to examine the influence of food on venlafaxine absorption fr om the 50-mg tablet. A standard, medium-fat breakfast eaten immediatel y before drug administration delayed the t(max) of venlafaxine but did not affect C-max or AUC. Therefore the tablet formulation of venlafax ine is bioequivalent to the oral solution, and the presence of food ap pears to decrease the rate but not the extent of absorption of venlafa xine from the tablet formulation.