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<p>The objective of this study was to compare the therapeutic and pharmacological performance of ivermectin (IVM) and fipronil (FIP) administered as single drugs, combined in a same formulation, or co-administered individually, as potential strategies to improve treatment efficacy against multi-resistant <i>Rhipicephalus microplus</i> populations. The effect of IVM dose escalation was also evaluated. Naturally infested heifers were allocated into six groups (G) and treated with: injectable IVM 1% at 0.2&#xa0;mg/kg (G-I) or 0.4&#xa0;mg/kg (G-II); FIP pour-on at 1&#xa0;mg/kg (G-III); pour-on formulation of IVM/FIP (0.5&#xa0;mg/kg IVM + 1&#xa0;mg/kg FIP; G-IV); co-administration of injectable IVM (0.2&#xa0;mg/kg) and pour-on FIP (1&#xa0;mg/kg; G-V); untreated (G-VI). IVM and FIP concentrations in plasma and ticks were quantified by HPLC. Absolute control was not achieved in any treated group. Therapeutic efficacy ranged from 66 to 82.6%, 88.0–97.3%, and 75.7–96.9% at days 3, 7, and 9 post-treatment, respectively, and outlier animals with high tick counts were consistently observed. Although significantly higher plasma IVM concentrations were achieved with the double dose, efficacy was not improved compared with the standard dose. Cattle treated with the pour-on combination showed markedly lower plasma IVM levels due to reduced topical absorption. Co-administration of individual drugs produced pharmacokinetic profiles similar to single-drug treatments. Neither IVM dose escalation nor IVM-FIP combinations improve therapeutic outcomes compared with those obtained with mono-drug formulations. When simultaneous use is required, co-administration of IVM and FIP is preferable to combined pour-on formulations because IVM absorption is better as injectable than in topical administration.</p>

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

  • 期刊论文

  • 发表日期：

    2026年2月25日

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  • Macarena Sarli,
  • María Victoria Rossner,
  • Jorgelina Torrents,
  • María Victoria Miró,
  • Adrián Lifschitz,
  • Santiago Nava

摘要

The objective of this study was to compare the therapeutic and pharmacological performance of ivermectin (IVM) and fipronil (FIP) administered as single drugs, combined in a same formulation, or co-administered individually, as potential strategies to improve treatment efficacy against multi-resistant Rhipicephalus microplus populations. The effect of IVM dose escalation was also evaluated. Naturally infested heifers were allocated into six groups (G) and treated with: injectable IVM 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 was not achieved in any treated group. Therapeutic efficacy ranged from 66 to 82.6%, 88.0–97.3%, and 75.7–96.9% at days 3, 7, and 9 post-treatment, respectively, and outlier animals with high tick counts were consistently observed. Although significantly higher plasma IVM concentrations were achieved with the double dose, efficacy was not improved compared with the standard dose. Cattle treated with the pour-on combination showed markedly lower plasma IVM levels due to reduced topical absorption. Co-administration of individual drugs produced pharmacokinetic profiles similar to single-drug treatments. Neither IVM dose escalation nor IVM-FIP combinations improve therapeutic outcomes compared with those obtained with mono-drug formulations. When simultaneous use is required, co-administration of IVM and FIP is preferable to combined pour-on formulations because IVM absorption is better as injectable than in topical administration.