The objectives of this study were to assess the effect of food and gender on the pharmacokinetics of avitripan. A group of 12 healthy men and 12 healthy women was administered a single 50 mg dose of avitriptan capsule under fasting conditions and 5 min after a high-fat breakfast. The two treatments were repeated in a replicate design to assess the intra-subject variability in the pharmacokinetics of avitriptan under fasted and fed conditions. There was a 1 week washout between treatments. Serial blood samples were collected over 24 h after dosing and analyzed by a validated HPLC method for avitriptan. The mean (SD) peak concentrations (Cmax) were 168 (86.4) ng mL-1 in the fasted condition and 57.3 (34.8) ng mL-1 in the fed condition in males and females combined. The corresponding areas under the plasma concentration curve (AUC) were 335 (162) and 185 (64.5) ng h mL-1, respectively. Both Cmax and AUC were significantly reduced in the fed condition. In addition, the time to peak concentration (tmax) was significantly delayed from a median of 45 min to 2 h after the high-fat breakfast. The clinical significance of this food effect is unclear at the present time. There were no gender differences nor a gender by food interaction in the pharmacokinetics of avitriptan. The intra- and inter-subject variability (%CV) in the Cmax and AUC of avitriptan in the fasted and fed conditions ranged from 10 to 60% in male and female subjects.