新規Thromboxane合成酵素阻害剤Sodium 4-[α-Hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3,5-dimethylbenzoate(Y-20811)の体内動態(第2報)イヌにおける未変化体及び主代謝物のPharmacokinetics

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The pharmacokinetics of sodium 4-[α-hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3,5-dimethylbenzoate (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-[α-hydroxy-2-hydroxymethyl-5-(1-imidazolyl) benzyl]-3,5-dimethylbenzoic 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.
公益社団法人日本薬学会の論文
1989-11-25