Resistant nematodes in cattle: Pharmaco-therapeutic assessment of the ivermectin- ricobendazole combination

CANDELA CANTON, LAURA CEBALLOS, CÉSAR FIEL, LAURA MORENO, PABLO DOMINGO YAGÜEZ, GISELE BERNAT, CARLOS LANUSSE, LUIS ALVAREZ

VETERINARY PARASITOLOGY

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2017 vol. 234 p. 40 - 48

0304-4017

Nematodicidal combinations have been proposed as a valid strategy to achieve effective nematodecontrol in the presence of drug resistance. The goals of this study were: (1) to compare the clinicalefficacy (therapeutic response) of ivermectin (IVM) and ricobendazole (RBZ) given subcutaneouslyeither by separate or combined administration to calves naturally infected with gastrointestinal nematodesresistant to IVM, and (2) to evaluate the potential pharmacokinetic (PK) and/or pharmacodynamic(PD) interactions occurring after the co-administration of both anthelmintics. Sixty male calves naturallyinfected with gastrointestinal nematodes resistant to IVM were randomly allocated into fourgroups (n = 15). Untreated control: animals not receiving anthelmintic treatment; IVM alone: animalstreated with IVM by subcutaneous (SC) injection (0.2 mg/kg); RBZ alone: animals received RBZ bythe SC route (3.75 mg/kg); IVM + RBZ: animals treated with IVM and RBZ (0.2 and 3.75 mg/kg, respectively),by SC injection in two separates sites. Eight animals of each treated group were randomlyselected to perform the PK study. Plasma samples were taken from those animals up to 28 days posttreatment.IVM and RBZ plasma concentrations were quantified by HPLC. The therapeutic responsewas determined by faecal egg count reduction test (FECRT). The proportions of third-stage larvae (L3)recovered from coprocultures were used to calculate the efficacy against the main parasite genera.The daily total egg deposition for each experimental group was estimated. Similar pharmacokinetictrends were obtained for both IVM and RBZ allying the single-drug and the combined treatments,which indicates the absence of PK interactions between both anthelmintics. The observed overall clinicaldrug efficacies were 48% (IVM alone), 94% (RBZ alone) and 98% (IVM + RBZ). Haemonchus spp.and Cooperia spp. were recovered in the coproculture after IVM treatment, suggesting that resistanceto IVM includes both genera. In fact, the efficacy against Cooperia spp. was 83% (IVM), 98% (RBZ)and 98% (IVM + RBZ), while the efficacy against Haemonchus spp. was 0% (IVM), 97% (RBZ) and 100%(IVM + RBZ). The combination was the only treatment that achieved 100% clinical efficacy against IVMresistantHaemonchus spp. The total egg excretion was reduced to 49.9% (IVM alone group), 6.3% (RBZalone group) and 1.8% (IVM + RBZ combined group) compared to the untreated control. Although thecombined treatment did not significantly increase the overall clinical efficacy in the current naturalfield conditions, an additive effect was achieved against IVM-resistant nematodes. In fact, the combinationobtained significantly higher efficacy against IVM-resistant Haemonchus spp. than RBZ alone.