CSIRO, Livestock Industries, Queensland Bioscience Precinct, Queensland, Australia.
Vet Parasitol. 2010 Mar 25;168(3-4):278-83. doi: 10.1016/j.vetpar.2009.11.002. Epub 2009 Nov 10.
The in vivo effect of dosing levamisole as a pulse release within an ivermectin (IVM) controlled-release device (CRD) was simulated by periodic dosing of levamisole to Haemonchus contortus-infected sheep already treated with an IVM CRD. The rationale for this treatment combination arises from the need to find alternative approaches to the treatment of gastrointestinal parasites in livestock in the face of increasing levels of anthelmintic resistance which is now widespread in Australia. Thirty merino sheep (4 months of age) were infected weekly with a mixture of susceptible and ivermectin resistant H. contortus beginning at Day 28. Twenty eight days after first infection, groups of 10 sheep were treated with IVM capsules alone, IVM capsules and an oral dose of levamisole (LEV) at Days 50 and 100 or no treatment. At pre-determined intervals, up to 126 days after treatment, faecal worm egg counts (FWEC) were determined and development rates of infective larvae (L3) cultured in faeces were measured. Haematological parameters and drug concentration in plasma were measured throughout the 100-day release period of the controlled-release device. Sheep were slaughtered at Day 135 for estimates of total worm burden. FWEC of sheep treated with IVM+LEV declined (99.9% reduction) after administration of oral LEV and were suppressed until Day 98. There was a significant difference (p<0.0001) in worm counts at slaughter between groups. The results demonstrate the potential advantage of combining a pulse of short-acting drug into the long-acting anthelmintic capsule to provide better parasite control than that achieved from the existing CRD treatment when IVM-resistant worms were present.
在伊维菌素（IVM）控释装置（CRD）中作为脉冲释放给药，体内给予左旋咪唑的效果通过已用 IVM CRD 处理的感染捻转血矛线虫的绵羊进行周期性左旋咪唑给药来模拟。这种治疗组合的原理源于在澳大利亚广泛存在抗寄生虫药物耐药性的情况下，寻找替代方法来治疗家畜胃肠道寄生虫的必要性。30 只美利奴羊（4 月龄）从第 28 天开始每周用敏感和伊维菌素耐药捻转血矛线虫混合物感染。首次感染后 28 天，每组 10 只绵羊分别用 IVM 胶囊单独治疗、IVM 胶囊和口服左旋咪唑（LEV）在第 50 天和 100 天治疗或不治疗。在预先确定的间隔内，在治疗后最多 126 天，测定粪便虫卵计数（FWEC），并测定粪便中感染性幼虫（L3）的发育率。在控释装置 100 天释放期间，测定血液学参数和血浆中药物浓度。绵羊在第 135 天屠宰，以估计总虫负荷。口服 LEV 给药后，用 IVM+LEV 治疗的绵羊的 FWEC 下降（99.9%减少），直到第 98 天才被抑制。屠宰时各组的虫数存在显著差异（p<0.0001）。结果表明，当存在 IVM 耐药虫时，将脉冲作用的短期药物组合到长效驱虫胶囊中，提供比现有 CRD 治疗更好的寄生虫控制，这具有潜在优势。
