PT  - JOURNAL ARTICLE
AU  - Randy C. Dockens
AU  - Kenneth S. Santone
AU  - James G. Mitroka
AU  - Richard A. Morrison
AU  - Mohammed Jemal
AU  - Douglas S. Greene
AU  - Rashmi H. Barbhaiya
TI  - Disposition of Radiolabeled Ifetroban in Rats, Dogs, Monkeys, and Humans
DP  - 2000 Aug 01
TA  - Drug Metabolism and Disposition
PG  - 973--980
VI  - 28
IP  - 8
4099  - http://dmd.aspetjournals.org/content/28/8/973.short
4100  - http://dmd.aspetjournals.org/content/28/8/973.full
SO  - Drug Metab Dispos2000 Aug 01; 28
AB  - Ifetroban is a potent and selective thromboxane receptor antagonist. This study was conducted to characterize the pharmacokinetics, absolute bioavailability, and disposition of ifetroban after i.v. and oral administrations of [14C]ifetroban or [3H]ifetroban in rats (3 mg/kg), dogs (1 mg/kg), monkeys (1 mg/kg), and humans (50 mg). The drug was rapidly absorbed after oral administration, with peak plasma concentrations occurring between 5 and 20 min across species. Plasma terminal elimination half-life was ∼8 h in rats, ∼20 h in dogs, ∼27 h in monkeys, and ∼22 h in humans. Based on the steady-state volume of distribution, the drug was extensively distributed in tissues. Absolute bioavailability was 25, 35, 23, and 48% in rats, dogs, monkeys, and humans, respectively. Renal excretion was a minor route of elimination in all species, with the majority of the dose being excreted into the feces. After a single oral dose, urinary excretion accounted for 3% of the administered dose in rats and dogs, 14% in monkeys, and 27% in humans, with the remainder excreted in the feces. Extensive biliary excretion was observed in rats with the hydroxylated metabolite at the C-14 position being the major metabolite observed in rat bile. Ifetroban was extensively metabolized after oral administration. Approximately 40 to 50% of the radioactivity in rat and dog plasma was accounted for by parent drug whereas, in humans, approximately 60% of the plasma radioactivity was accounted for by ifetroban acylglucuronide. The American Society for Pharmacology and Experimental Therapeutics