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 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.
Marathe
P H
PH
Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Company, Princeton, NJ, USA. Punit_H._Marathe@ccmail.bms.com
Greene
D S
DS
Lee
J S
JS
Barbhaiya
R H
RH
D000328:Adult; D002214:Capsules; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000494:pharmacology*; D005215:Fasting / Q000378:metabolism; D005260:Female; D005502:Food; D006801:Humans; D007206:Individuality; D007211:Indoles / Q000493:pharmacokinetics*; D008297:Male; D012702:Serotonin Antagonists / Q000493:pharmacokinetics*; D012737:Sex Factors; D013449:Sulfonamides / Q000493:pharmacokinetics*; D014363:Tryptamines
D002214:Capsules; D004041:Dietary Fats; D007211:Indoles; D012702:Serotonin Antagonists; D013449:Sulfonamides; D014363:Tryptamines; C103231:avitriptan