雄性大鼠口服36Cl-奥硝唑后的代谢及其抗生育活性

Metabolism of 36Cl-ornidazole after oral application to the male rat in relation to its antifertility activity.

Jones A R, Cooper T G

Department of Biochemistry, University of Sydney, NSW, Australia.

Xenobiotica. 1997 Jul;27(7):711-21. doi: 10.1080/004982597240299.

Abstract

The antimycotic ornidazole (a male antifertility agent in rats) was synthesized incorporating 36Cl in the chloropropyl sidechain and its metabolism was investigated in the male rat after oral ingestion. 2. Blood levels of radioactivity were low over the first 24 h and there was no tissue accumulation of radioactivity over 48 h. 3. Most of the excreted radioactivity (20% of the ingested dose) appeared in the urine within the first 24 h. 4. Three major compounds were detected in 0-24-h urine samples and were characterized as ornidazole (13% of total radioactivity), Cl- (22%) and 3-chlorolactate (30%), the oxidation product of 3-chlorolactaldehyde. 5. No polyuria or glucosuria was observed following the oral administration of ornidazole, suggesting that any (R)-3-chlorolactate produced was insufficient to affect renal metabolism. 6. Conversion of ornidazole initially to (R, S)-alpha-chlorohydrin or ultimately to the glycolytic inhibitor (S)-3-chlorolactaldehyde could explain its antifertility action in the male rat.

摘要

抗真菌药奥硝唑（一种对大鼠有雄性抗生育作用的药物）通过在氯丙基侧链中引入³⁶Cl进行合成，并在雄性大鼠口服后研究其代谢情况。2. 在最初的24小时内，血液中的放射性水平较低，并且在48小时内没有放射性在组织中的积累。3. 大部分排泄出的放射性（摄入剂量的20%）在最初的24小时内出现在尿液中。4. 在0 - 24小时的尿液样本中检测到三种主要化合物，分别鉴定为奥硝唑（占总放射性的13%）、Cl⁻（22%）和3 - 氯乳酸（30%），3 - 氯乳酸是3 - 氯乙醛的氧化产物。5. 口服奥硝唑后未观察到多尿或糖尿现象，这表明所产生的任何（R）-3 - 氯乳酸不足以影响肾脏代谢。6. 奥硝唑最初转化为（R，S）-α - 氯醇或最终转化为糖酵解抑制剂（S）-3 - 氯乙醛可以解释其对雄性大鼠的抗生育作用。