Zacchei A G, Wishousky T I, Arison B H, Hitzenberger G
Drug Metab Dispos. 1978 May-Jun;6(3):303-12.
The metabolism of the polyvalent saluretic agent (2-cyclopentyl-6,7-dichloro-2-methyl-1-oxo-5-indanyloxy)acetic acid was studied in chimpanzee and man. The drug was well absorbed and extensively metabolized by man. Peak levels of drug (5--8 microgram/ml) occurred within 1.5--4.5 hr of drug administration. The plasma half-life was estimated to be 2 hr; a similar half-life was observed in the chimpanzee. Little unchanged drug (less than 10%) was excreted in the urine of either species. Similar metabolic profiles were obtained for man and chimpanzee. The major urinary metabolites resulted from hydroxylation of the cyclopentyl moiety, giving rise to a number of diastereomers. The alcohol metabolites were subsequently oxidized to the ketone. The excretion of the metabolites coincided with maximal excretion of sodium and chloride ions. The hydroxylated metabolites have intrinsic pharmacological activity.
对多价利尿素（2-环戊基-6,7-二氯-2-甲基-1-氧代-5-茚满氧基）乙酸在黑猩猩和人类体内的代谢情况进行了研究。该药物在人体内吸收良好且代谢广泛。给药后1.5至4.5小时内出现药物峰值水平（5 - 8微克/毫升）。血浆半衰期估计为2小时；在黑猩猩中观察到类似的半衰期。两种物种的尿液中排泄的未变化药物均很少（不到10%）。人类和黑猩猩获得了相似的代谢谱。主要的尿液代谢产物是环戊基部分羟基化产生的，产生了多种非对映异构体。醇类代谢产物随后被氧化为酮。代谢产物的排泄与钠和氯离子的最大排泄量一致。羟基化代谢产物具有内在的药理活性。
