Assessment of effect of food, gender, and intra-subject variability in the pharmacokinetics of avitriptan

✍ Scribed by P. H. Marathe; D. S. Greene; J. S. Lee; R. H. Barbhaiya

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 129 KB
• Volume: 19
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/(sici)1099-081x(199804)19:3<153::aid-bdd90>3.0.co;2-t

✦ Synopsis

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 (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 combined. The corresponding areas under the plasma concentration curve (AUC) 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 addition, 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 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 C max and AUC of avitriptan in the fasted and fed conditions ranged from 10 to 60% in male and female subjects.