Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba, Argentina.
Cátedra de Farmacología y Toxicología, Facultad de Ciencias Agropecuarias, Universidad Católica de Córdoba - Unidad Ejecutora IRNASUS, UCC-CONICET, Córdoba, Argentina.
J Pharm Pharmacol. 2018 Jan;70(1):51-58. doi: 10.1111/jphp.12834. Epub 2017 Oct 16.
Here, we aimed to assess the pharmacokinetic performance and therapeutic response (anthelmintic efficacy) of an albendazole (ABZ) nano-sized formulation in dogs.
In the pharmacokinetic study, ABZ self-dispersible nanocrystals (SDNCS) and a control formulation were administered orally to healthy dogs (n = 6). The concentrations of the sulphoxide metabolite in plasma were determined by high-performance liquid chromatography. For the anthelmintic efficacy trial, SDNCS and a commercially available formulation of ABZ were given to naturally parasitised dogs. The number of Ancylostoma caninum eggs in the faeces was determined using the McMaster technique.
The area under the curve, Tmax and Cmax for the SDNCS were improved compared to the control. The efficacy study showed no statistical differences between the SDNCS and the commercial formulation at the doses of 25 and 12.5 mg/kg. However, significant differences (P < 0.05) between the treatments were found at 6.25 mg/kg (a quarter of the reference dose) with a reduction in the faecal nematode egg counts of 62.0 ± 21.1% and 100 ± 0% for the control and SDNCS, respectively.
The improved pharmacokinetic performance observed for the novel formulation of ABZ correlated with an improved in vivo therapeutic response against a model intestinal nematode parasite in dogs.
本研究旨在评估阿苯达唑（ABZ）纳米制剂在犬体内的药代动力学性能和治疗反应（驱虫疗效）。
在药代动力学研究中，将 ABZ 自分散纳米晶体（SDNCS）和对照制剂以口服方式给予健康犬（n=6）。通过高效液相色谱法测定血浆中亚砜代谢物的浓度。在驱虫疗效试验中，将 SDNCS 和市售 ABZ 制剂给予自然感染的犬。使用麦克马斯特技术测定粪便中Ancylostoma caninum 卵的数量。
与对照制剂相比，SDNCS 的曲线下面积、Tmax 和 Cmax 得到改善。在 25 和 12.5 mg/kg 剂量下，SDNCS 与市售制剂之间的疗效研究无统计学差异。然而，在 6.25 mg/kg（参考剂量的四分之一）剂量下，两种治疗方法之间存在显著差异（P<0.05），对照制剂和 SDNCS 的粪便线虫卵计数分别减少了 62.0±21.1%和 100±0%。
新型 ABZ 制剂观察到的改善药代动力学性能与犬模型肠道线虫寄生虫的体内治疗反应改善相关。
