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头孢喹肟在绵羊单次和重复皮下给药后的药代动力学

Pharmacokinetics of cefquinome after single and repeated subcutaneous administrations in sheep.

作者信息

Corum Orhan, Corum Duygu Durna, Er Ayse, Uney Kamil

机构信息

Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Kastamonu, Kastamonu, Turkey.

Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Selcuk, Konya, Turkey.

出版信息

J Vet Pharmacol Ther. 2019 Nov;42(6):647-653. doi: 10.1111/jvp.12750. Epub 2019 Feb 4.

Abstract

The purpose of this study was to determine the pharmacokinetics of cefquinome (CFQ) following single and repeated subcutaneous (SC) administrations in sheep. Six clinically healthy, 1.5 ± 0.2 years sheep were used for the study. In pharmacokinetic study, the crossover design in three periods was performed. The withdrawal interval between the study periods was 15 days. In first period, CFQ (Cobactan, 2.5%) was administered by an intravenous (IV) bolus (3 sheep) and SC (3 sheep) injections at 2.5 mg/kg dose. In second period, the treatment administration was repeated via the opposite administration route. In third period, CFQ was administrated subcutaneously to each sheep (n = 6) at a dose of 2.5 mg/kg q. 24 hr for 5 days. Plasma concentrations of CFQ were measured using the HPLC-UV method. Pharmacokinetic parameters were calculated using non-compartmental methods. The elimination half-life and mean residence time of CFQ after the single SC administration were longer than IV administration (p < 0.05). Bioavailability (F%) of CFQ following the single SC administration was 123.51 ± 11.54%. The area under the curve (AUC ) and peak concentration following repeated doses (last dose) were higher than those observed after the first dose (p < 0.05). CFQ accumulated after repeated SC doses. CFQ can be given via SC at a dose of 2.5 mg/kg every 24 hr for the treatment of infections caused by susceptible pathogens, which minimum inhibitory concentration is ≤1.0 μg/ml in sheep.

摘要

本研究的目的是确定头孢喹肟(CFQ)在绵羊单次和重复皮下(SC)给药后的药代动力学。选用6只临床健康、年龄为1.5±0.2岁的绵羊进行本研究。在药代动力学研究中,采用了三个阶段的交叉设计。研究阶段之间的停药间隔为15天。在第一阶段,以2.5mg/kg的剂量通过静脉推注(3只绵羊)和皮下注射(3只绵羊)给予CFQ(Cobactan,2.5%)。在第二阶段,通过相反的给药途径重复进行治疗给药。在第三阶段,以2.5mg/kg的剂量每24小时给每只绵羊(n=6)皮下注射CFQ,持续5天。采用高效液相色谱-紫外法测定CFQ的血浆浓度。使用非房室方法计算药代动力学参数。单次皮下给药后CFQ的消除半衰期和平均驻留时间长于静脉给药(p<0.05)。单次皮下给药后CFQ的生物利用度(F%)为123.51±11.54%。重复给药(最后一剂)后的曲线下面积(AUC)和峰浓度高于首次给药后观察到的值(p<0.05)。重复皮下给药后CFQ会蓄积。CFQ可以每24小时以2.5mg/kg的剂量通过皮下给药,用于治疗由对绵羊最小抑菌浓度≤1.0μg/ml的敏感病原体引起的感染。

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