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The pharmacokinetics of sodium 4-[alpha-hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3,5-dimethylbenzoat e (I-Na) in the beagle dog was investigated after p.o. and i.v. administration. After the administration of I-Na at 3 mg/kg (p.o.), 70.9% of the dose was absorbed, and the maximum plasma concentration of free acid (I) was observed at 0.33 h. After p.o. administration, the area under the plasma concentration-time curve of I increased almost linearly in proportion to the dose. The metabolite, 4-[alpha-hydroxy-2-hydroxymethyl-5-(1-imidazolyl)benzyl]-3,5-dimethyl benzoic acid (II) was also detected in the plasma, but the concentration of II was lower than that of I. After the administration at 3 mg/kg (p.o.), 27.7% and 3.8% of the dose were recovered as I and II, respectively, in the urine, and 32.2% and 30.1% recovered as I and II in the feces. Therefore, 93.8% of the dose was totally recovered within five days. The inhibitory effect of II on the aggregation of rabbit platelets was studied in vitro. This metabolite showed only one sixth activity of I-Na. Thus, the inhibitory effect on the platelet aggregation of II is considered to be almost negligible in the beagle dog administered with I-Na.

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Pharmacokinetics of Sodium 4-[&amp;alpha;-Hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3, 5-dimethylbenzoate (Y-20811), a New Thromboxane Synthetase Inhibitor. II. Pharmacokinetics of Intact Drug and Main Metabolite in Dog