Studies on the Pharmacokinetics of Ebselen in Rats (3): Absorption, Distribution and Excretion after Administration of 75Se-labelled Compound.

Abstract

In order to clarify whether ebselen, 2-phenyl-1, 2-benzisoselenazol-3(2H)-one is metabolized to liberate its selenium atom as an inorganic compound(s) or not in vivo, blood level of radioactivity and excretion of radioactivity in urine and feces were determined, and whole body autoradiograms were prepared after oral administration of 75Se-ebselen (50 mg/kg) or intravenous injection of Na275SeO3, an inorganic selenium compound, as a control (1 mg/kg) to male rats. Following results were obtained: 1. For 75Se-ebselen dosing group, the mean blood levels of radioactivity reached the Cmax of 29.17 nmol eq. to ebselen/ml (8.00 μg eq./ml) at 1 hr and declined with a half-life, t1/2 of 7.6 hr from 2 to 24 hr after dosing. For Na275SeO3 dosing group, the blood level of radioactivity was 57.75 nmol eq. to Na275SeO3/ml (9.99 μgeq./ml) at the first sampling time and thereafter declined slowly with a half-life, t1/2 of 190 hr from 24 to 168 hr after dosing. 2. For 75Se-ebselen dosing group, the highest levels of radioactivity were observed in the gastric and intestinal contents, followed by fat, brown fat and liver, showing higher radioactivity than that in blood. The overall distribution of radioactivity decreased with time and the radioactivity was not detected at 168 hr after dosing. For Na275SeO3 dosing group, high levels of radioactivity remained in liver, kidney and blood even at 168 hr after dosing. 3. For 75Se-ebselen dosing group, within 168 hr after dosing, 53.8% of the dosed radioactivity was excreted in urine, and 45.8% of that in feces. The residual radioactivity in the carcass was not detected. For Na275SeO3 dosing group, within 168 hr after dosing, 44.8% of the dosed radioactivity was excreted in urine, and 8.0% of that in feces. The radioactivity remained in the carcass, being 41.1% of the dose. From the results above, the extent of inorganic selenium release from ebselen was estimated to be 0.0% of the dose.