ASSESSMENT OF EFFECT OF FOOD, GENDER, AND INTRA-SUBJECT VARIABILITY IN THE PHARMACOKINETICS OF AVITRIPTAN

The objectives of this study were to assess the effect of food and gen der on the pharmacokinetics of avitripan. A group of 12 healthy men an d 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 treatmen ts. Serial blood samples were collected over 24 h after dosing and ana lyzed by a validated HPLC method for avitriptan. The mean (SD) peak co ncentrations (C-max) 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 c ombined. The corresponding areas under the plasma concentration curve (AUG) were 335 (162) and 185 (64.5) ng h mL(-1), respectively. Both C- max and AUC were significantly reduced in the fed condition. In additi on, the time to peak concentration (t(max)) was significantly delayed from a median of 45 min to 2 h after the high-fat breakfast. The clini cal significance of this food effect is unclear at the present time. T here were no gender differences nor a gender by food interaction in th e pharmacokinetics of avitriptan. The intra-and inter-subject variabil ity (%CV) in the C-max and AUC of avitriptan in the fasted and fed con ditions ranged from 10 to 60% in male and female subjects. (C) 1998 Jo hn Wiley & Sons, Ltd.