Jauch R, Kopitar Z, Hammer R, Prox A, Fricke H
Arzneimittelforschung. 1975;25(12):1947-54.
Blood and plasma levels as well as urinary and fecal excretion were measured in humans after oral administration of radioactively labelled 4-[j-(2'-fluorobiphenylyl)]-4-hydroxycrotonic acid (S-H 766 MO). The radioactivity in the plasma reaches maximum values of about 10 mug eq./ml 1 to 2 h after application with either form. After repeated administration good agreement is found between the plasma levels measured and those simulated according to the pharmacokinetic parameters obtained after single application. The S-H 766 metabolites were investigated in blood and urine. The substance was found to undergo considerable metabolism, only approximately 2% being excreted in the urine unchanged. The conjugates, which constitute over 60% of the radioactivity of the urine, consist mainly of glucuronides and sulfates. The structure of the aglycones shows that the metabolism occurs along two pathways, by beta-oxidation of the aliphatic side chain into aryl acetic acids and by hydroxylation of the aromatic nucleus to phenolic compounds. It must be assumed that these biotransformations take place both simultaneously and successively.
在人体口服放射性标记的4-[j-(2'-氟联苯基)]-4-羟基巴豆酸（S-H 766 MO）后，对血液和血浆水平以及尿液和粪便排泄进行了测量。无论以何种形式给药，血浆中的放射性在给药后1至2小时达到约10微克当量/毫升的最大值。多次给药后，所测血浆水平与根据单次给药后获得的药代动力学参数模拟的血浆水平之间具有良好的一致性。对血液和尿液中的S-H 766代谢产物进行了研究。发现该物质会发生大量代谢，只有约2%以原形从尿液中排泄。占尿液放射性60%以上的结合物主要由葡糖醛酸苷和硫酸盐组成。苷元的结构表明，代谢沿着两条途径发生，通过脂肪族侧链的β-氧化生成芳基乙酸，以及通过芳环的羟基化生成酚类化合物。必须假定这些生物转化同时且相继发生。
