PHARMACOKINETICS OF ONCE-DAILY VENLAFAXINE EXTENDED-RELEASE IN HEALTHY-VOLUNTEERS

Three pharmacokinetics studies were performed to assess the effects of food intake and morning versus evening administration of once-daily v enlafaxine extended release (XR) on the pharmacokinetic disposition of venlafaxine and its active metabolite O-desmethylvenlafaxine (ODV). F orty-six healthy adults (43 men and 3 women), 18 to 45 years of age wi th body weight within 15% of normal for height and frame, were enrolle d in these studies. In two studies, venlafaxine XR 75-mg or 150-mg cap sules were administered to healthy subjects in a fasting state or afte r 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 mornin g or in the evening. All three studies were conducted with a two-perio d cross-over study design, and the plasma samples were assayed using h igh-performance liquid chromatography for the concentrations of venlaf axine 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 formulatio n exhibits a controlled rate of release, and administration of venlafa xine XR with a high-fat meal does not produce a dose-dumping effect. B ased 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 system ic exposure to venlafaxine and ODV.