CEVA Santé Animale, Preclinical Department, La Ballastiere, BP 126-33501 Libourne Cedex, France.
Res Vet Sci. 2010 Apr;88(2):307-14. doi: 10.1016/j.rvsc.2009.09.001. Epub 2009 Nov 30.
Colistin is an antimicrobial drug of the polymyxin group and COLIVET SOLUTION is an aqueous solution containing colistin sulphate (2 x 10(6) IU/mL), formulated for oral administration. The target species is the pig, particularly the suckling and post weaning animal. This investigation was undertaken to provide pharmacokinetic and pharmacodynamic data on which to base the selection of dosage rate and interval of the solution for the treatment of porcine colibacillosis. Colistin absorption from the gastrointestinal tract of young pigs, when administered at dosage rates of 25,000, 50,000 and 100,000 IU/kg, was slight or absent. The drug was therefore restricted almost entirely to the required site of action. The colistin concentration-time profile within the jejunum and ileum was established, and this enabled determination of the pharmacokinetic variables, maximum concentration (C(max)) and area under curve (AUC) and derivation of the surrogate indices of antibacterial activity, C(max)/minimum inhibitory concentration (MIC) and AUC/MIC through integration of in vivo data with the results of in vitro potency studies for four strains of Escherichia coli. In the in vitro bacterial growth inhibition studies colistin acted by a concentration-dependent killing mechanism. Numerical values for the surrogate parameter AUC/MIC producing bactericidal and eradication effects of colistin against four strains of E. coli were established by PK-PD modeling based on the sigmoidal E(max) equation. These data were used to predict a daily dosage regimen for colistin.
黏菌素是多黏菌素类抗菌药物，COLIVET SOLUTION 是一种含有硫酸黏菌素（2 x 10(6) IU/mL）的水溶液，用于口服给药。目标物种是猪，特别是哺乳和断奶后的动物。进行这项研究是为了提供药代动力学和药效学数据，以便为治疗猪大肠杆菌病选择该溶液的剂量率和间隔提供依据。当以 25,000、50,000 和 100,000 IU/kg 的剂量率给小猪胃肠道给药时，几乎完全不存在从胃肠道吸收黏菌素。因此，该药物几乎完全局限于所需的作用部位。在空肠和回肠中建立了黏菌素的浓度-时间曲线，从而确定了药代动力学变量、最大浓度（C(max)）和曲线下面积（AUC），并通过将体内数据与体外效力研究的结果整合，推导出抗菌活性的替代指数 C(max)/最低抑菌浓度（MIC）和 AUC/MIC。在体外细菌生长抑制研究中，黏菌素通过浓度依赖性杀菌机制发挥作用。通过基于 sigmoidal E(max)方程的 PK-PD 模型，建立了针对 4 株大肠杆菌的黏菌素产生杀菌和根除作用的替代参数 AUC/MIC 的数值。这些数据用于预测黏菌素的每日剂量方案。
