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在恒河猴(猕猴)中口服和肌肉注射恩诺沙星后,对恩诺沙星及其活性代谢物环丙沙星进行的药代动力学研究。

A pharmacokinetic study of enrofloxacin and its active metabolite ciprofloxacin after oral and intramuscular dosing of enrofloxacin in rhesus monkeys (Macaca mulatta).

作者信息

Klein Hilton, Hasselschwert Dana, Handt Larry, Kastello Michael

机构信息

Merck & Co. Inc., West Point, PA, USA.

出版信息

J Med Primatol. 2008 Aug;37(4):177-83. doi: 10.1111/j.1600-0684.2008.00280.x. Epub 2008 Mar 31.

Abstract

Enrofloxacin is used for treating Shigellosis in non-human primates; however, there are no reports describing its pharmacokinetics in rhesus monkeys. Pharmacokinetic data in intended target species (rhesus) help to determine the proper dose regimen. Blood levels of enrofloxacin and ciprofloxacin (enrofloxacin's active metabolite), were determined after either intramuscular or oral dosing of enrofloxacin for 7 days in a cross-over study. Levels of both antibiotics were determined by solid phase extraction followed by reversed-phase chromatography with tandem mass spectrometry. Results indicate enrofloxacin half-life after intramuscular dosing is estimated to be 2.4 hours. Enrofloxacin given either intramuscular or p.o. rapidly achieves satisfactory therapeutic blood levels of enrofloxacin or ciprofloxacin in rhesus monkeys. Results from these pharmacokinetic study parallel values published for other animal species. Our results show use of enrofloxacin is effective in managing Shigella infections in rhesus monkeys based upon achieving these blood drug levels.

摘要

恩诺沙星用于治疗非人灵长类动物的志贺氏菌病;然而,尚无关于其在恒河猴体内药代动力学的报道。目标物种(恒河猴)的药代动力学数据有助于确定合适的给药方案。在一项交叉研究中,对恒河猴连续7天进行肌肉注射或口服恩诺沙星后,测定了恩诺沙星和环丙沙星(恩诺沙星的活性代谢物)的血药浓度。两种抗生素的浓度通过固相萃取后,采用反相色谱-串联质谱法测定。结果表明,肌肉注射后恩诺沙星的半衰期估计为2.4小时。肌肉注射或口服恩诺沙星后,恒河猴体内能迅速达到令人满意的恩诺沙星或环丙沙星治疗血药浓度。这些药代动力学研究结果与其他动物物种公布的数值相似。我们的结果表明,基于达到这些血药浓度,使用恩诺沙星治疗恒河猴志贺氏菌感染是有效的。

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