Segre G, Fiaschi A I, Bianchi E, Ciani D, Tedeschi S
Institute of Pharmacology, University of Siena, Italy.
Arzneimittelforschung. 1988 Dec;38(12):1846-9.
The kinetics of rosaprostol (9-hydroxy-19,20-bis-norprostanoic acid, Rosal) and of its metabolite (3-(2-n-hexyl-5-hydroxy-cyclopentyl)propionic acid) has been determined in plasma and in urine of 10 healthy volunteers after oral administration of 500 mg of rosaprostol. The peak of rosaprostol (of 524 ng/ml) appears at 4 h, whereas that of the metabolite (of 503 ng/ml) appears earlier (2 h); therefore the relationship between the two substances does not follow the precursor-successor relationship in plasma and a compartmental model has been used to fit the data. In this model the biotransformation process occurs before entering the central compartment (first-pass effect). The mean half-life of rosaprostol is equal to about 5 h and that of the metabolite is equal to 3 h. All of rosaprostol is biotransformed and only the metabolite is partially eliminated by the urine. The urinary excretion of the metabolite represents only a small fraction of the administered dose. The urinary clearance of the metabolite is equal to 5.3 l/h. The volume of distribution of both substances is equal to 21.2 l.
在10名健康志愿者口服500毫克罗沙前列醇后，测定了罗沙前列醇（9-羟基-19,20-双去甲前列腺酸，Rosal）及其代谢产物（3-(2-正己基-5-羟基环戊基)丙酸）在血浆和尿液中的动力学。罗沙前列醇的峰值（524纳克/毫升）出现在4小时，而代谢产物的峰值（503纳克/毫升）出现得更早（2小时）；因此，这两种物质在血浆中的关系并不遵循前体-后继关系，已使用房室模型来拟合数据。在该模型中，生物转化过程在进入中央房室之前发生（首过效应）。罗沙前列醇的平均半衰期约为5小时，代谢产物的平均半衰期为3小时。所有罗沙前列醇都发生了生物转化，只有代谢产物部分经尿液排出。代谢产物的尿排泄量仅占给药剂量的一小部分。代谢产物的尿清除率为5.3升/小时。两种物质的分布容积均为21.2升。
