Brodie R R, Chasseaud L F, Elson F F, Franklin E R, Taylor T
Arzneimittelforschung. 1976;26(5):896-901.
The excretion and plasma concentrations of radioactivity and chromatographic patterns of radioactive components in plasma and excreta have been compared in rats, dogs and man after oral doses of the hypolipidemic agent isopropyl-[4'-(p-chlorobenzoyl)-2-phenoxy-2-methyl]-propionate (LF 178; procetofene; Lipanthyl¿). 2. In rats, 48.1% of a single dose of 25 mg/kg was excreted in the urine, and 48.6% in the faeces. In dogs, 23.1% of a single dose at the same level was excreted in the urine, and 71.8% in the faeces, but 88.1% of a dose of 300 mg to man was excreted in the urine, and only 5.1% in the faeces. Peak levels of radioactivity in the plasma of all three species studied were similar (20--30 mug/ml) after doses at these levels and concentrations declined thereafter with half-lives of 7--24 h in rats and dogs, and 7 h in man. The half-life of radioactivity concentrations in rat plasma was not altered by repeated daily doses for 7 days. 3. Whole-body autoradiography of rats showed that radioactivity was largely associated with the liver, kidneys and gut, which are the organs of biotransformation and excretion, although relatively high levels were present in lungs and blood, and small amounts of radioactivity had a widespread distribution into some peripheral tissues during 2--7 h after dosing. 4. The available chromatographic evidence indicated that the most important biotransformation pathway appeared to be ester hydrolysis to LF 178 acid and formation of water soluble conjugates of this acid. This pathway appeared similar to that of the related drug clofibrate (ethyl p-chlorophenoxyisobutyrate).
给大鼠、狗和人口服降血脂药物异丙基-[4'-(对氯苯甲酰基)-2-苯氧基-2-甲基]-丙酸酯（LF 178；普罗布考；力平之®）后，比较了放射性的排泄和血浆浓度以及血浆和排泄物中放射性成分的色谱图。2. 在大鼠中，单次给予25 mg/kg剂量后，48.1%经尿液排泄，48.6%经粪便排泄。在狗中，相同剂量水平下单次给药的23.1%经尿液排泄，71.8%经粪便排泄，但给予人300 mg剂量时，88.1%经尿液排泄，仅5.1%经粪便排泄。在所研究的所有三个物种中，这些剂量水平下血浆中放射性的峰值水平相似（20 - 30 μg/ml），此后浓度下降，大鼠和狗的半衰期为7 - 24小时，人的半衰期为7小时。大鼠血浆中放射性浓度的半衰期不受连续7天每日重复给药的影响。3. 对大鼠的全身放射自显影显示，放射性主要与肝脏、肾脏和肠道相关，这些是生物转化和排泄器官，尽管肺部和血液中也存在相对较高水平，给药后2 - 7小时少量放射性广泛分布到一些外周组织中。4. 现有的色谱证据表明，最重要的生物转化途径似乎是酯水解为LF 178酸并形成该酸的水溶性结合物。该途径似乎与相关药物氯贝丁酯（对氯苯氧异丁酸乙酯）的途径相似。
