PT  - JOURNAL ARTICLE
AU  - P. H. Marathe
AU  - D. S. Greene
AU  - R. H. Barbhaiya
TI  - Disposition of [<sup>14</sup>C]Avitriptan in Rats and Humans
DP  - 1997 Jul 01
TA  - Drug Metabolism and Disposition
PG  - 881--97
VI  - 25
IP  - 7
4099  - http://dmd.aspetjournals.org/content/25/7/881.short
4100  - http://dmd.aspetjournals.org/content/25/7/881.full
SO  - Drug Metab Dispos1997 Jul 01; 25
AB  - Avitriptan is a new 5-HT1-like agonist with abortive antimigraine properties. The study was conducted to characterize the pharmacokinetics, absolute bioavailability, and disposition of avitriptan after intravenous (iv) and oral administrations of [14C]avitriptan in rats and oral administration of [14C]avitriptan in humans. The doses used were 20 mg/kg iv and oral in the rat, 10 mg iv in humans, and 50 mg oral in humans. The drug was rapidly absorbed after oral administration, with peak plasma concentrations occurring at 0.5 hr postdose. Absolute bioavailability was 19.3% in rats and 17.2% in humans. Renal excretion was a minor route of elimination in both species, with the majority of the dose being excreted in the feces. After a single oral dose, urinary excretion accounted for 10% of the administered dose in rats and 18% of the administered dose in humans, with the remainder excreted in the feces. Extensive biliary excretion was observed in rats. Avitriptan was extensively metabolized after oral administration, with the unchanged drug accounting for 32% and 22% of the total radioactivity in plasma in rats and humans, respectively. Plasma terminal elimination half-life was ∼1 hr in rats and ∼5 hr in humans. The drug was extensively distributed in rat tissues, with a tendency to accumulate in the pigmented tissues of the eye. The American Society for Pharmacology and Experimental Therapeutics