Pharmacokinetics of once-daily venlafaxine extended release in healthy volunteers

Abstract

Three pharmacokinetic studies were performed to assess the effects of food intake and morning versus evening administration of once-daily venlafaxine extended release (XR) on the pharmacokinetic disposition of venlafaxine and its active metabolite O-desmethylvenlafaxine (ODV). Forty-six healthy adults (43 men and 3 women), 18 to 45 years of age with body weight within 15% of normal for height and frame, were enrolled in these studies. In two studies, venlafaxine XR 75-mg or 150-mg capsules were administered to healthy subjects in fasting state or after a high-fat breakfast. In a third study, once-daily venlafaxine XR 75 mg was administered for 4 days (to steady state) either in the morning or in the evening. All three studies were conducted with a two-period crossover study design, and the plasma samples were assayed using high-performance liquid chromatography for the concentrations of venlafaxine and ODV. The steady-state pharmacokinetic profile of venlafaxine XR was not affected by the time of administration (morning or evening), and the single-dose pharmacokinetic profile was not affected by the presence or absence of food. Therefore, the venlafaxine XR formulation exhibits a controlled rate of release, and administration of venlafaxine XR with a high-fat meal does not produce a dose-dumping effect. Based on the results of these studies in healthy volunteers, once-daily venlafaxine XR 75 or 150 mg may be given without regard to meals and once-daily venlafaxine XR 75 mg may be taken either in the morning or evening without affecting the pharmacokinetic disposition of or systemic exposure to venlafaxine and ODV.