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恩诺沙星在健康和感染大肠杆菌的肉鸡中的组织分布及处置动力学

Tissue distribution and disposition kinetics of enrofloxacin in healthy and E. coli infected broilers.

作者信息

Soliman G A

机构信息

Pharmacology Department, Faculty of Veterinary Medicine, Cairo University, Egypt.

出版信息

Dtsch Tierarztl Wochenschr. 2000 Jan;107(1):23-7.

Abstract

Concentrations of enrofloxacin equivalent activity were determined by microbiological assay in the plasma of healthy and E. coli-infected broilers following single intravenous and oral administrations at 10 mg/kg. Tissue distribution and residue-depletion following multiple oral doses (10 mg/kg for 3 successive days) were investigated. Pharmacokinetic variables were determined using compartmental and non-compartmental analytical methods. Plasma enrofloxacin concentrations after intravenous dosing to healthy and infected birds were best described by a two-compartments model. Enrofloxacin concentrations in plasma of infected birds were lower than those of healthy ones. The disposition kinetics of intravenously administered drug in healthy and infected birds were somewhat different. The elimination half-life (t1/2 beta) was 4.75 vs. 3.63 h; mean residence time (MRT) was 6.72 vs 4.90 h; apparent volume of the central compartment (Vc) was 1.11 vs 1.57 l/kg; rate constant for transfer from peripheral to central compartment (k21) was 1.15 vs 1.41 h-1 and total body clearance (ClB) was 0.35 vs 0.53 l/h/kg in healthy and infected birds, respectively. After oral administration, the absorption half-life (t1/2abs) in the infected birds was significantly longer than in healthy birds, while elimination half-life (t1/2el) and MRT were significantly shorter. Bioavailability was higher in infected birds (72.50%) as compared to healthy ones (69.78%). Enrofloxacin was detected in the tissues of healthy and infected birds after daily oral dosing of 10 mg/kg for 3 days. It was more concentrated in liver, kidney, and breast muscle. The minimal inhibitory concentration (MIC) of enrofloxacin against E. coli was 0.064 microgram/ml. On the basis of maintaining enrofloxacin plasma concentrations over the MIC, a dose of 10 mg/kg given intravenously every 20.14 hrs or orally every 20.86 hrs should provide tissue concentrations effective against E. coli infection in chickens.

摘要

在健康肉鸡和感染大肠杆菌的肉鸡单次静脉注射和口服10 mg/kg恩诺沙星后,通过微生物学测定法测定血浆中恩诺沙星等效活性浓度。研究了多次口服给药(连续3天每天10 mg/kg)后的组织分布和残留消除情况。使用房室和非房室分析方法确定药代动力学变量。静脉注射给药后,健康鸡和感染鸡血浆中的恩诺沙星浓度最好用二室模型描述。感染鸡血浆中的恩诺沙星浓度低于健康鸡。健康鸡和感染鸡静脉注射药物的处置动力学有所不同。消除半衰期(t1/2β)分别为4.75小时和3.63小时;平均驻留时间(MRT)分别为6.72小时和4.90小时;中央房室表观容积(Vc)分别为1.11 l/kg和1.57 l/kg;从周边房室向中央房室转移的速率常数(k21)分别为1.15 h-1和1.41 h-1,健康鸡和感染鸡的总体清除率(ClB)分别为0.35 l/h/kg和0.53 l/h/kg。口服给药后,感染鸡的吸收半衰期(t1/2abs)明显长于健康鸡,而消除半衰期(t1/2el)和MRT明显较短。感染鸡的生物利用度(72.50%)高于健康鸡(69.78%)。在每天口服10 mg/kg连续3天后,在健康鸡和感染鸡的组织中均检测到恩诺沙星。它在肝脏、肾脏和胸肌中浓度更高。恩诺沙星对大肠杆菌的最低抑菌浓度(MIC)为0.064微克/毫升。基于维持血浆中恩诺沙星浓度高于MIC,每20.14小时静脉注射10 mg/kg或每20.86小时口服一次该剂量应能提供对鸡大肠杆菌感染有效的组织浓度。

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