Pharmacokinetic Studies of Betotastine Besilate (TAU-284). (I): Absorption, Distribution, Metabolism and Excretion after a Single Oral Administration.

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The absorption, distribution, metabolism and excretion were studied following a single oral administration of 14C-TAU-284 to rats and dogs. 1. The blood level of radioactivity increased within 30min, reaching the Cmax of 0.27μg eq./ml, and was decreased with a t1/2 (1-8 hr) of 3 hrs after oral administration of 14C-TAU-284 to male rats. 2. The level of radioactivity in almost tissue was attained the maximum 30 minutes after oral administration. In these tissues, the levels in liver was highest, followed by kidney, small intestine, stomach, gall bladder, pancreas and adrenal gland. The levels in other tissues were the same as plasma level or lower. The decrease of radioactivity in most tissues was similar to that in plasma. 3. The autoradiograms of pigment rats at 24 hrs after dosing, the distribution of radioactivity in the skin and the uveal-tract of eyes, melanin containing tissues, was observed. The radioactivity in these tissues was disappeared 30 days after dosing. 4. The unchanged drug was major component found in urine and bile. In rat urine, only β-oxidative metabolite was detected. In rat bile, taurine-conjugated metabolite of the unchanged drug and 5 other metabolites were detected. No metabolite was detected in plasma of rat and dog and in the urine of dog. 5. Urinary and fecal excretion were 39.7 and 61.6%, of the dosed radioactivity, respectively, within 120 hrs after oral administration to male rats. Biliary excretion accounted for 40.6% of the dose and its possible that most of it was subjected to entero-hepatic circulation.