Antiallergic chromones. I. Disposition of 5-(3- p-cyanophenoxy-2-hydroxy-1-propoxy)-2-(1 H-tetrazol-5-yl) chromone in four mammalian species

Abstract

The gastrointestinal absorption, plasma concentrations, excretion, and metabolism of the 14C-labeled sodium salt of 5-(3-p-cyanophenoxy-2-hydroxy-1-propoxy)-2-(1H-tetrazol-5-yl) chromone (NaCPTC) were studied in rats, mice, dogs, and monkeys. In addition, tissue distribution of [14C]NaCPTC was studied in rats. All animals received a single po or iv 10 mg/kg dose of [14C]NaCPTC. In each species, the decline of plasma concentrations was rapid after iv dosing and 14C was quickly excreted in urine and bile. The highest tissue 14C concentrations were found in liver. Plasma 14C concentrations after po administration were very low, relative to those after iv administration in all species. The estimated extent of gastro-intestinal absorption was about 10.4, 9.6, 9.9, and 3.6% in the rat, mouse, dog, and monkey, respectively. Fecal excretion was the preferred route of drug elimination, and excretion appeared to be essentially complete in three of the four species within 48 hr. In analyses of plasma and urine samples from the four species conducted by reverse phase high pressure liquid chromatography, no evidence of metabolism of NaCPTC was found.