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两种不同两性霉素B制剂在健康犬体内药代动力学特征的比较。

Comparison of the pharmacokinetic profiles of two different amphotericin B formulations in healthy dogs.

作者信息

Bingöl B, Bakirel T

机构信息

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

出版信息

J Vet Pharmacol Ther. 2018 Feb;41(1):e16-e21. doi: 10.1111/jvp.12446. Epub 2017 Aug 16.

Abstract

This study was conducted to compare the pharmacokinetic profiles of conventional (Fungizone ) and liposomal amphotericin B (AmBisome ) formulations in order to predict their therapeutic properties, and evaluate their potential differences in veterinary treatment. For this purpose, twelve healthy mixed breed dogs received both drugs at a dose of 0.6 mg/kg by intravenous infusion over a 4-min period in a total volume of 40 ml. Blood samples were collected at 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 48, 72 and 96 hr after dosing, and concentrations of drug in plasma were determined by high-performance liquid chromatography (HPLC). Pharmacokinetics was described by a two-compartment model. Although both formulations were administered at the same doses (0.6 mg/kg), the plasma pharmacokinetics of liposomal amphotericin B differed significantly from those of amphotericin B deoxycholate in healthy dogs (p < .05). Liposomal amphotericin B showed markedly higher peak plasma concentrations (approximately ninefold greater) and higher area under the plasma concentration curve values (approximately 14-fold higher) compared to conventional formulation. It is concluded that AmBisome reached higher plasma concentration and lower distribution volume and had a longer half-life compared to Fungizone , and therefore, AmBisome is reported to be an appropriate and effective choice for the treatment of systemic mycotic infections in dogs.

摘要

本研究旨在比较传统制剂(两性霉素B)和脂质体两性霉素B(安必素)的药代动力学特征,以预测它们的治疗特性,并评估它们在兽医治疗中的潜在差异。为此,12只健康的杂种犬在4分钟内静脉输注40毫升总体积的两种药物,剂量均为0.6毫克/千克。给药后0、0.5、1、1.5、2、3、4、8、12、24、48、72和96小时采集血样,采用高效液相色谱法(HPLC)测定血浆中药物浓度。药代动力学用二室模型描述。尽管两种制剂的给药剂量相同(0.6毫克/千克),但脂质体两性霉素B在健康犬中的血浆药代动力学与去氧胆酸盐两性霉素B有显著差异(p<0.05)。与传统制剂相比,脂质体两性霉素B的血浆峰浓度明显更高(约高9倍),血浆浓度曲线下面积值也更高(约高14倍)。结论是,与两性霉素B相比,安必素达到更高的血浆浓度和更低的分布容积,半衰期更长,因此,据报道安必素是治疗犬全身性真菌感染的合适且有效的选择。

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