Absorption, distribution and excretion of [14C]E-4716 after single-dose administration in rats and dogs

The absorption, distribution and excretion of E-4716, a novel antihistamine, were studied in rats and dogs after single-dose oral or intravenous administration of [14C]E-4716. Radioactivity was rapidly and efficiently absorbed from the gastrointesanal tract after oral administration, and biphasic plasma concentration-time profiles were observed in both species. In rats, oral absorption was linear within the dose range studied, and no differences in administration route or doses were observed in elimination. Elimination was approximately twice as fast in dogs as in rats. No sex differences in elimination were observed in dogs. Radioactivity was widely distributed in rats, and levels in brain, eyes, fat and testes were lower than those in plasma. Excretion was mainly by feces in rats and by urine in dogs, showing species differences. After oral administration in rats, unchanged drug was rapidly absorbed and the absolute bioavailability was only 20%, suggesting an important first-pass effect.