Maffei Facino R, Carini M, Tofanetti O
Arzneimittelforschung. 1986 Apr;36(4):722-8.
The metabolism of the hypolipidemic agent 1,10-bis(hydroxyethylthio)decane (tiadenol, Eulip) has been studied in vivo in man and in the rat and in vitro in the rat. Following oral administration, in both species tiadenol was completely absorbed, extensively metabolized by the liver and more than 95% of the dose was eliminated in this form via kidneys within 48 h. Insignificant was the excretion of the unchanged drug in urine (approximately 1%) as well as that of its metabolites in the feces. 8 metabolites were isolated from human or rat urine and their structures were elucidated by means of electron impact, field desorption and positive and negative fast atom bombardment mass spectrometry. Both in man and in the rat the main metabolic pathway was the oxidation of the thioether sulfur, followed by oxidation or conjugation of the primary alcohol group(s). The urinary excretion of S-oxidized metabolites and sulfoxidized carboxylic metabolites accounted for 75% of the dose and that of S-oxidized conjugated metabolites for 20%. Rat in vitro studies showed that hepatic microsomal cytochrome P-450-dependent monooxygenase catalyzes the S-oxidative pathway, which governs the in vivo elimination of the drug in both species. Thus cytochrome P-450 is the key enzyme in the hepatic detoxification of tiadenol.
已在人体和大鼠体内以及大鼠体外对降血脂药物1,10 - 双（羟乙硫基）癸烷（硫癸醇，Eulip）的代谢进行了研究。口服给药后，在这两个物种中硫癸醇均被完全吸收，在肝脏中广泛代谢，超过95%的剂量在48小时内通过肾脏以这种形式排出。药物原形在尿液中的排泄量极少（约1%），其代谢产物在粪便中的排泄量也极少。从人或大鼠尿液中分离出8种代谢产物，并通过电子轰击、场解吸以及正、负离子快原子轰击质谱法阐明了它们的结构。在人体和大鼠中，主要的代谢途径都是硫醚硫的氧化，随后是伯醇基团的氧化或结合。S - 氧化代谢产物和硫氧化羧酸代谢产物的尿排泄量占剂量的75%，S - 氧化结合代谢产物的尿排泄量占20%。大鼠体外研究表明，肝微粒体细胞色素P - 450依赖性单加氧酶催化S - 氧化途径，该途径决定了这两个物种体内药物的消除。因此，细胞色素P - 450是硫癸醇肝脏解毒过程中的关键酶。
