DISPOSITION OF [C-14] AVITRIPTAN IN RATS AND HUMANS

Avitriptan is a new 5-HT1-like agonist with abortive antimigraine prop erties. The study was conducted to characterize the pharmacokinetics, absolute bioavailability, and disposition of avitriptan after intraven ous (iv) and oral administrations of [C-14]avitriptan in rats and oral administration of [C-14]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 hu mans. The drug was rapidly absorbed after oral administration, with pe ak plasma concentrations occurring at 0.5 hr postdose. Absolute bioava ilability 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 ex cretion accounted for 10% of the administered dose in rats and 18% of the administered dose in humans, with the remainder excreted in the fe ces. 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 i n rats and humans, respectively. Plasma terminal elimination half-life was similar to 1 hr in rats and similar to 5 hr in humans. The drug w as extensively distributed in rat tissues, with a tendency to accumula te in the pigmented tissues of the eye.