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拟议的“立体类似效应”解释了环丙沙星对恩诺沙星抗生素代谢的减缓作用及其机制。

A proposed "steric-like effect" for the slowdown of enrofloxacin antibiotic metabolism by ciprofloxacin, and its mechanism.

机构信息

National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.

Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, Madrid, 28040, Spain.

出版信息

Chemosphere. 2021 Dec;284:131347. doi: 10.1016/j.chemosphere.2021.131347. Epub 2021 Jun 28.

Abstract

The results of monitoring over the years have shown that the mixing and coexistence of various low-level antibiotic residual pollutants has increased significantly, among which, the problems of enrofloxacin (ENR) and ciprofloxacin (CIP) were more prominent. At present, research studies on the metabolism of ENR or CIP are focused on the individual drugs, and there is no relevant research reporting on the effect of the combination of the two antibiotics on the metabolism of ENR. This research study evaluated the effect of CIP on ENR metabolism in pigs and its mechanism in vivo and in vitro. The results showed that CIP changed the pharmacokinetics of ENR through the inhibition of CYP3A29 and the "steric-like effect" of ENR binding to CYP3A29, which increased the residual concentration of ENR in pigs, a result that requires an extension of the withdrawal period. In order to ensure human health, the combined use of these two drugs, CIP and ENR, must be avoided in veterinary medicine in food producing animals.

摘要

多年来的监测结果表明,各种低水平抗生素残留污染物的混合共存现象明显增多,其中恩诺沙星(ENR)和环丙沙星(CIP)的问题更为突出。目前,关于 ENR 或 CIP 的代谢研究主要集中在单一药物上,尚无相关研究报道两种抗生素联合使用对 ENR 代谢的影响。本研究评估了 CIP 对猪体内和体外 ENR 代谢的影响及其作用机制。结果表明,CIP 通过抑制 CYP3A29 和 ENR 与 CYP3A29 的“空间位阻样效应”改变了 ENR 的药代动力学,增加了猪体内 ENR 的残留浓度,这需要延长停药期。为了保障人类健康,在食用动物的兽医用药中必须避免这两种药物,即 CIP 和 ENR 的联合使用。

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