Suárez G, Alvarez L, Castells D, Correa O, Fagiolino P, Lanusse C
Laboratorio de Farmacología, Universidad de la República (UDELAR), Montevideo, Uruguay.
J Vet Pharmacol Ther. 2011 Dec;34(6):557-64. doi: 10.1111/j.1365-2885.2011.01274.x. Epub 2011 Mar 3.
A pharmaco-parasitological assessment of four different albendazole (ABZ) formulations was carried out in lambs infected with multiple resistant gastrointestinal (GI) nematodes. The comparative drug systemic exposure profiles (ABZ sulphoxide plasma concentrations) and anthelmintic efficacies (clinical endpoint measured through the faecal nematode eggs reduction counts) were determined for a reference formulation (RF) and three different test (T1, T2, T3) generic ABZ preparations. Fifty (50) Corriedale lambs naturally infected with multiple resistant GI nematodes were allocated into five experimental groups (n = 10). Animals in each group received treatment with either the RF, one of the test ABZ formulations (5 mg/kg by the intraruminal route) or were kept as untreated control. Blood samples were collected over 48 h post-treatment. ABZ parent drug was not recovered in the bloodstream. The ABZ sulphoxide (ABZSO) and sulphone (ABZSO(2) ) metabolites were measured in plasma by ultraviolet high-performance liquid chromatography over 36-48 h post-treatment. A faecal nematode egg count reduction test (FECRT) was performed at day 10th post-treatment to lambs from all treated and untreated groups, which indicated the predominance of nematodes with high level of resistance to ABZ. Both ABZSO C(max) and AUC(0-LOQ) values obtained for the RF (pioneer product) were significantly higher (P < 0.05) than those obtained for the T1 and T3 preparations. Based on the currently available bioequivalence criteria, the test (generic) ABZ formulations under evaluation could not be considered equivalent to the RF regarding the rate (C(max) ) and extent (AUC(0-LOD) ) of drug absorption (indirectly estimated through the ABZSO metabolite). A large variation in nematode egg counts did not permit to obtain statistically significant differences among formulations. However, a favourable trend in the efficacy against the most resistant nematodes was observed for the formulations with the highest ABZSO systemic exposure.
对感染多种耐药胃肠道线虫的羔羊进行了四种不同阿苯达唑（ABZ）制剂的药物寄生虫学评估。测定了一种参比制剂（RF）和三种不同的试验（T1、T2、T3）通用ABZ制剂的药物全身暴露情况（阿苯达唑亚砜血浆浓度）和驱虫效果（通过粪便线虫卵减少计数测量的临床终点）。将50只自然感染多种耐药胃肠道线虫的考力代羔羊分为五个实验组（n = 10）。每组动物接受参比制剂、一种试验性ABZ制剂（瘤胃内途径给药，剂量为5mg/kg）治疗，或作为未治疗对照。治疗后48小时内采集血样。血液中未检测到阿苯达唑原药。治疗后36 - 48小时内，通过紫外高效液相色谱法测定血浆中的阿苯达唑亚砜（ABZSO）和砜（ABZSO₂）代谢物。在治疗后第10天对所有治疗组和未治疗组的羔羊进行粪便线虫卵计数减少试验（FECRT），结果表明对阿苯达唑耐药水平高的线虫占优势。参比制剂（原研产品）的ABZSO Cmax和AUC(0-LOQ)值显著高于T1和T3制剂（P < 0.05）。根据目前可用的生物等效性标准，就药物吸收的速率（Cmax）和程度（AUC(0-LOD)）而言（通过ABZSO代谢物间接估计），所评估的试验性（通用）ABZ制剂不能被认为与参比制剂等效。线虫卵计数的巨大差异使得无法在制剂之间获得统计学上的显著差异。然而，对于ABZSO全身暴露最高的制剂，在对抗耐药性最强的线虫方面观察到了有利趋势。
