Davison C, Benziger D, Fritz A, Edelson J
Drug Metab Dispos. 1975 Nov-Dec;3(6):520-4.
2-[4-(2,2-Dichlorocyclopropyl)phenoxy]-2-methylpropanoic acid, Win 35,833, was readily absorbed after oral administration; in rats, rhesus monkeys, and human volunteers, peak concentrations of drug in plasma were attained within 2 hr of medication. The time-concentration curve of administered drug was biphasic in monkeys and men, while in rats the kinetics of a one-compartment model were observed. Distribution studies of 14C-labeled drug in the rat showed that most of the radioactivity was excreted in the feces and that significant quantities of 14C were sequestered by depot fat. Monkeys and human subjects both eliminated Win 35,833 primarily through the kidneys. The drug was excreted in rat bile and human urine, both as the free acid and conjugated with glucuronic acid. At physiological concentrations, Win 35,833 was extensively bound to rat, monkey, and human plasma proteins. A gas-chromatographic method for the analysis of drug in plasma, urine, or bile gave a linear relationship between peak height ratios and concentrations, in the range of 1-60 mug/ml.
2-[4-(2,2-二氯环丙基)苯氧基]-2-甲基丙酸（Win 35,833）口服给药后易于吸收；在大鼠、恒河猴和人类志愿者中，服药后2小时内血浆中药物浓度达到峰值。给药药物的时间-浓度曲线在猴子和人类中呈双相，而在大鼠中观察到单室模型的动力学。对大鼠体内14C标记药物的分布研究表明，大部分放射性物质通过粪便排出，并且大量14C被储存脂肪所摄取。猴子和人类受试者主要通过肾脏消除Win 35,833。该药物以游离酸形式以及与葡萄糖醛酸结合的形式经大鼠胆汁和人类尿液排出。在生理浓度下，Win 35,833与大鼠、猴子和人类血浆蛋白广泛结合。一种用于分析血浆、尿液或胆汁中药物的气相色谱法在1-60微克/毫升范围内，峰高比与浓度之间呈线性关系。
