替卡西林在大鼠、狗和人体内的代谢。

The metabolism of talampicillin in rat, dog and man.

Jeffery D J, Jones K H, Langley P F

Xenobiotica. 1978 Jul;8(7):419-27. doi: 10.3109/00498257809070026.

Abstract

After administration of [phthalidyl-14C] talampicillin (Talpen) to rat, dog and man, radioactivity was excreted mainly in the urine (90%, 86% and 98% in rat, dog and man respectively). 2. After administration of [ampicillin-14C] talampicillin, radioactivity was excreted in the urine of rats and dogs to a lesser extent (35% in both species) and only a small proportion of the dose was excreted in the bile (6% in rats, less than 0.1% in dogs). 3. The pattern of radiometabolites was very similar in extracts of the urines of radiometabolites was very similar in extracts of the urines of rat, dog and man dosed orally with [phthalidyl-14C]talampicillin. The major metabolite was 2-hydroxymethylbenzoic acid. 4. Unchanged talampicillin was present in the hepatic portal vein blood of dog and thus reached the liver, whereas in rat, no parent compound could be detected in portal vein blood. This result may help to explain differences in toxicity of the compound in rat and dog. 5. Studies in vitro showed that the intestinal wall is an important site of hydrolysis of talampicillin in rat and dog.

摘要

给大鼠、狗和人服用[邻苯二甲酰基 - 14C]酞氨苄青霉素（Talpen）后，放射性物质主要经尿液排出（大鼠、狗和人分别为90%、86%和98%）。2. 服用[氨苄青霉素 - 14C]酞氨苄青霉素后，大鼠和狗尿液中放射性物质的排出量较少（两种动物均为35%），且仅有一小部分剂量经胆汁排出（大鼠为6%，狗小于0.1%）。3. 给大鼠、狗和人口服[邻苯二甲酰基 - 14C]酞氨苄青霉素后，其尿提取物中放射性代谢物的模式非常相似。主要代谢物为2 - 羟甲基苯甲酸。4. 酞氨苄青霉素原形存在于狗的肝门静脉血液中，因此可到达肝脏，而在大鼠的门静脉血液中未检测到母体化合物。这一结果可能有助于解释该化合物在大鼠和狗体内毒性的差异。5. 体外研究表明，肠壁是大鼠和狗体内酞氨苄青霉素水解的重要部位。