Interspecies variation in the metabolism of zoniporide by aldehyde oxidase
Interspecies variation in the metabolism of zoniporide by aldehyde oxidase
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DOI：
10.3109/00498254.2012.727499
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发表时间：
2013-05-01
期刊：
影响因子：
1.8
通讯作者：
Zhou, Sue
中科院分区：
文献类型：
--
作者：
Dalvie, Deepak;Xiang, Cathie;Zhou, Sue
1. 醛氧化酶（AO）是一种细胞质酶，参与人类和临床前物种的异种生物I期代谢。目前的研究利用S9组分探讨了佐硝普胺在各种动物和人体内的体外代谢。动物种类包括常用的药理学和毒理学模型和家畜，如猫、牛或牛、猪和马。此外，还探讨了部分物种的性别差异和品系差异。除狗和猫外，所有动物均将氮唑吡嗪转化为2-氧唑吡嗪（M1）。Michael-Menten动力学研究在将佐硝普啉转化为M1.6的物种中进行。zonporide氧化过程中K-M、V-max和Cl-int有显著差异。虽然人类S9中氮唑吡嗪氧化的K-M和V-max在男性和女性中相似，但在动物中却存在一些性别差异，尤其是在V-max中。家畜AO活性和对佐硝普胺的亲和力也存在明显的物种差异。
1. Aldehyde oxidase (AO) is a cytosolic enzyme that contributes to the Phase I metabolism of xenobiotics in human and preclinical species.2. Current studies explored in vitro metabolism of zoniporide in various animal species and humans using S9 fractions. The animal species included commonly used pharmacology and toxicology models and domestic animals such as the cat, cow or bull, pig and horse.3. In addition, gender and strain differences in some species were also explored.4. All animals except the dog and cat converted zoniporide to 2-oxozoniporide (M1).5. Michael-Menten kinetic studies were conducted in species that turned over zoniporide to M1.6. Marked differences in K-M, V-max and Cl-int were observed in the oxidation of zoniporide.7. Although the K-M and V-max of zoniporide oxidation in male and female human S9 was similar, some gender difference was observed in animals especially, in V-max.8. The domestic animals also showed marked species differences in the AO activity and affinity toward zoniporide.