Butyrophenone系薬物に関する生物薬剤学的研究(第4報)Clofluperolのラットにおける体内動態の性差

抄録

The metabolism of clofluperol by liver microsomes from both male and female Wistar rats was studied using ³H-labelled clofluperol. p-Fluoro-o-tritiobenzoylpropionic acid was the only radioactive metabolite formed from the microsomal metabolism of ³H-clofluperol. The apparent V_max value for its metabolism by the liver microsomes of male rats was two times greater than that by female rats, while such difference was not shown in the apparent K_m value. The effect of castration and pretreatment with SKF 525-A on the distribution of ³H in the blood, brain, liver, adrenal, and pancreas of male rats was studied after dosing ³H-clofluperol (0.3 mg/kg) orally. Concentration of ³H in the blood and adrenal of castrated male rats and those in all tissues examined of SKF 525-A-pretreated male rats were generally higher than those in the corresponding tissues of intact male rats. These results suggest that clofluperol ingested is first N-dealkylated by the microsomal drug-metabolizing enzyme of the liver, and the sex difference observed in the disposition of clofluperol may depend on the extent of its metabolism in the liver.