环氧司坦在大鼠的药代动力学

大鼠灌胃(ig)环氧司坦三种剂量50,100及200 mg·kg^-1后,测定12 h的血药浓度,根据各鼠血药浓度—时间数据拟合曲线,均呈一室动力学模型。其Ka分别为0.578 h^-1,0.553 h^-1,0.439 h^-1;K分别为0.308 h^-1,0.282 h^-1,0.224 h^-1;T_1/2分别为2.27 h,2.54 h,3.12 h;AUC分别为786.89,1644.43和3335.35 μg·h^-1·ml^-1。组织中以肾上腺、肝、胃肠、生殖器(子宫与卵巢)为高,其次是肾、心、脑、肺、脾,高峰浓度在3 h左右,与血药浓度分布情况一致。三种剂量的血浆蛋白结合率均在90%左右,结合率与给药剂量无关。原形药在胆汁、尿及粪便中排泄百分率甚少。提示大部分药物可能在体内进行转化。

PHARMACOKINETICS OF EPOSTANE IN RATS

After rats were given (ig) epostane 50, 100 and 200 mg·kg^-1, plasma concentrations of epostane were determined by HPLC. According to concentration versus time data, the pharmacokinetic model of epostane in all rats followed a pattern of one-compartment model. The pharmacokinetic parameters of the three doses were found to be as follows: Ka were 0. 578 h^-1, 0.553 h^-1 and 0. 439 h^-1; K were 0. 308 h^-1, 0. 282 h^-1 and 0. 224 h^-1; T_1/2 were 2. 27 h, 2. 54 h, 3. 12 h and AUC were 786. 89μg· h·ml^-1, 1644. 43μg · h · ml^-1, and 3335. 35 μg· h^-1·ml^-1 respectively.The tissue distribution of epostane in rats were as follows: highest in adrenal, liver, gastrointestinal tract, uterus and ovary; next in kidney, heart, brain, lung and spleen. The peak concentration times were about 3 h and comparable to plasma peak time. Plasma protein binding of epostane was determined by equilibrant dialysis of the plasma of rats given the drug and found that the degree of binding was not correlated with drug dosage under our experimental conditions. Little epostane was found in the bile, urine and feces. It appears that epostane might have undergone extensive biotransformation in the rat body.