Evaluation of dose escalation and drug combinations of ivermectin and fipronil as strategies for improving control of resistant Rhipicephalus microplus populations

The objective of this study was to compare the therapeutic and pharmacological performance of ivermectin (IVM) andfipronil (FIP) administered as single drugs, combined in a same formulation, or co-administered individually, as potentialstrategies to improve treatment efficacy against multi-resistant Rhipicephalus microplus populations. The effect of IVMdose escalation was also evaluated. Naturally infested heifers were allocated into six groups (G) and treated with: injectableIVM 1% at 0.2 mg/kg (G-I) or 0.4 mg/kg (G-II); FIP pour-on at 1 mg/kg (G-III); pour-on formulation of IVM/FIP (0.5 mg/kg IVM + 1 mg/kg FIP; G-IV); co-administration of injectable IVM (0.2 mg/kg) and pour-on FIP (1 mg/kg;G-V); untreated (G-VI). IVM and FIP concentrations in plasma and ticks were quantified by HPLC. Absolute control wasnot achieved in any treated group. Therapeutic efficacy ranged from 66 to 82.6%, 88.0–97.3%, and 75.7–96.9% at days3, 7, and 9 post-treatment, respectively, and outlier animals with high tick counts were consistently observed. Althoughsignificantly higher plasma IVM concentrations were achieved with the double dose, efficacy was not improved comparedwith the standard dose. Cattle treated with the pour-on combination showed markedly lower plasma IVM levels due toreduced topical absorption. Co-administration of individual drugs produced pharmacokinetic profiles similar to singledrugtreatments. Neither IVM dose escalation nor IVM-FIP combinations improve therapeutic outcomes compared withthose obtained with mono-drug formulations. When simultaneous use is required, co-administration of IVM and FIP ispreferable to combined pour-on formulations because IVM absorption is better as injectable than in topical administration. Fil: Sarli, Macarena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación de la Cadena Láctea. - Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Rafaela. Instituto de Investigación de la Cadena Láctea; Argentina Fil: Rossner, Maria Victoria. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Chaco-Formosa. Estación Experimental Agropecuaria Colonia Benítez; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación de la Cadena Láctea. - Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Rafaela. Instituto de Investigación de la Cadena Láctea; Argentina