Laboratorio de Farmacología, Centro de Investigación Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Facultad de Ciencias Veterinarias, Campus Universitario, 7000, Tandil, Argentina.
Laboratorio de Farmacología, Centro de Investigación Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Facultad de Ciencias Veterinarias, Campus Universitario, 7000, Tandil, Argentina.
Int J Parasitol Drugs Drug Resist. 2021 Apr;15:162-167. doi: 10.1016/j.ijpddr.2021.03.003. Epub 2021 Mar 22.
The goal of the current work was to perform an integrated evaluation of monepantel (MNP) pharmacokinetics (PK) and pharmacodynamics, measured as anthelmintic efficacy, after its oral administration to calves naturally infected with GI nematodes resistant to ivermectin (IVM) and ricobendazole (RBZ) on three commercial farms. On each farm, forty-five calves were randomly allocated into three groups (n = 15): MNP oral administration (2.5 mg/kg); IVM subcutaneous (SC) administration (0.2 mg/kg); and RBZ SC administration (3.75 mg/kg). Eight animals from the MNP treated group (Farm 1) were selected to perform the PK study. Drug concentrations were measured by HPLC. The efficacy was determined by the faecal egg count reduction test (FECRT). MNP and MNP-sulphone (MNPSO) were the main analytes recovered in plasma. MNPSO systemic exposure was markedly higher compared to that obtained for MNP. Higher Cmax and AUC values were obtained for the active MNPSO metabolite (96.8 ± 29.7 ng/mL and 9220 ± 1720 ng h/mL) compared to MNP (21.5 ± 4.62 ng/mL and 1709 ± 651 ng h/mL). The MNPSO AUC value was 6-fold higher compared to the parent drug. Efficacies of 99% (Farm 1), 96% (Farm 2) and 98% (Farm 3) demonstrated the high activity of MNP (P < 0.05) against GI nematodes resistant to IVM (reductions between 27 and 68%) and RBZ (overall efficacy of 75% on Farm 3). While IVM failed to control Haemonchus spp. and Cooperia spp., and RBZ failed to control Coooperia spp. and Ostertagia spp., MNP achieved 100% efficacy against Haemonchus spp., Cooperia spp. and Ostertagia spp. However, a low efficacy of MNP against Oesophagostomum spp. (efficacies ranging from 22 to 74%) was observed. In conclusion, oral treatment with MNP should be considered for dealing with IVM and benzimidazole resistant nematode parasites in cattle. The work described here reports for the first time an integrated assessment of MNP pharmaco-therapeutic features and highlights the need to be considered as a highly valuable tool to manage nematode resistant to other chemical families.
当前的工作旨在对在三个商业农场中自然感染 GI 线虫且对伊维菌素（IVM）和苯并咪唑（RBZ）具有抗药性的小牛进行口服莫能菌素（MNP）药代动力学（PK）和药效学的综合评估，其药效学表现为驱虫效果。在每个农场中，将 45 头小牛随机分为三组（n=15）：MNP 口服给药（2.5mg/kg）；IVM 皮下（SC）给药（0.2mg/kg）；RBZ SC 给药（3.75mg/kg）。从 MNP 治疗组（农场 1）中选择 8 只动物进行 PK 研究。通过 HPLC 测量药物浓度。通过粪便卵计数减少试验（FECRT）确定疗效。在血浆中回收了 MNP 和 MNP-砜（MNPSO）为主的分析物。与 MNP 相比，MNPSO 的全身暴露明显更高。与 MNP（21.5±4.62ng/mL 和 1709±651ng h/mL）相比，活性 MNPSO 代谢物（96.8±29.7ng/mL 和 9220±1720ng h/mL）的 Cmax 和 AUC 值更高。MNPSO AUC 值是母体药物的 6 倍。99%（农场 1），96%（农场 2）和 98%（农场 3）的疗效表明 MNP 对 IVM（27%至 68%的减少）和 RBZ（农场 3 的总体疗效为 75%）具有抗 GI 线虫的高活性，对 IVM 具有抗药性。（总体疗效为 75%）和 RBZ（农场 3）。虽然 IVM 未能控制 Haemonchus spp.和 Cooperia spp.，RBZ 未能控制 Coooperia spp.和 Ostertagia spp.，但 MNP 对 Haemonchus spp.、Cooperia spp.和 Ostertagia spp.的疗效达到 100%。然而，MNP 对 Oesophagostomum spp.的疗效较低（疗效范围为 22%至 74%）。总的来说，口服 MNP 治疗可用于治疗牛的 IVM 和苯并咪唑耐药线虫寄生虫。这里描述的工作首次综合评估了 MNP 的药物治疗特性，并强调需要将其视为管理对其他化学家族具有抗药性的线虫的极具价值的工具。
