犬类中盐酸环丙沙星的药代动力学及普通盐酸环丙沙星片的口服吸收情况

Ciprofloxacin pharmacokinetics and oral absorption of generic ciprofloxacin tablets in dogs.

作者信息

Papich Mark G

机构信息

Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607, USA.

出版信息

Am J Vet Res. 2012 Jul;73(7):1085-91. doi: 10.2460/ajvr.73.7.1085.

DOI:10.2460/ajvr.73.7.1085

PMID:22738062

Abstract

OBJECTIVE

To determine the pharmacokinetics of ciprofloxacin in dogs, including oral absorption following administration of generic ciprofloxacin tablets.

ANIMALS

6 healthy Beagles.

PROCEDURES

In a crossover study design, ciprofloxacin was administered as a generic tablet (250 mg, PO; mean dose, 23 mg/kg) and solution (10 mg/kg, IV) to 6 dogs. In a separate experiment, 4 of the dogs received ciprofloxacin solution (10 mg/mL) PO via stomach tube (total dose, 250 mg). Blood samples were collected before (time 0) and for 24 hours after each dose. Plasma concentrations were analyzed with high-pressure liquid chromatography. Pharmacokinetic analysis was performed by means of compartmental modeling.

RESULTS

When ciprofloxacin was administered as tablets PO, peak plasma concentration was 4.4 μg/mL (coefficient of variation [CV], 55.9%), terminal half-life (t(1/2)) was 2.6 hours (CV, 10.8%), area under the time-concentration curve was 22.5 μg•h/mL (CV, 62.3%), and systemic absorption was 58.4% (CV, 45.4%). For the dose administered IV, t(1/2) was 3.7 hours (CV, 52.3%), clearance was 0.588 L/kg/h (CV, 33.9%), and volume of distribution was 2.39 L/kg (CV, 23.7%). After PO administration as a solution versus IV administration, plasma concentrations were more uniform and consistent among dogs, with absorption of 71% (CV, 7.3%), t(1/2) of 3.1 hours (CV, 18.6%), and peak plasma concentration of 4.67 μg/mL (CV, 17.6%).

CONCLUSIONS AND CLINICAL RELEVANCE

Inconsistent oral absorption of ciprofloxacin in some dogs may be formulation dependent and affected by tablet dissolution in the small intestine. Because of the wide range in oral absorption of tablets, the dose needed to reach the pharmacokinetic-pharmacodynamic target concentration in this study ranged from 12 to 52 mg/kg (CV, 102%), with a mean dose of 25 mg/kg, once daily, for bacteria with a minimum inhibitory concentration ≤ 0.25 μg/mL.

摘要

目的

测定环丙沙星在犬体内的药代动力学，包括给予普通环丙沙星片剂后的口服吸收情况。

动物

6只健康的比格犬。

方法

采用交叉研究设计，给6只犬分别口服普通片剂（250 mg，经口给药；平均剂量，23 mg/kg）和溶液（10 mg/kg，静脉注射）。在另一项实验中，4只犬通过胃管经口给予环丙沙星溶液（10 mg/mL）（总剂量，250 mg）。在每次给药前（0时）和给药后24小时采集血样。采用高压液相色谱法分析血浆浓度。通过房室模型进行药代动力学分析。

结果

当环丙沙星以片剂经口给药时，血浆峰浓度为4.4 μg/mL（变异系数[CV]，55.9%），末端半衰期（t(1/2)）为2.6小时（CV，10.8%），时间-浓度曲线下面积为22.5 μg•h/mL（CV，62.3%），全身吸收率为58.4%（CV，45.4%）。对于静脉注射剂量，t(1/2)为3.7小时（CV，52.3%），清除率为0.588 L/kg/h（CV，33.9%），分布容积为2.39 L/kg（CV，23.7%）。与静脉注射相比，经口给予溶液后，犬体内血浆浓度在个体间更均匀、更一致，吸收率为71%（CV，7.3%），t(1/2)为3.1小时（CV，18.6%），血浆峰浓度为4.67 μg/mL（CV，17.6%）。