Failure of doramectin and ivermectin in preventing Cochliomyia hominivorax myiasis in a subtropical region: A pharmacokinetic-pharmacodynamic study

The aim of this work is to present a case study where the failure of IVM 3.15 % and DRM 1 % to prevent natural infestations of C. hominivorax larvae in Argentina is investigated based on field efficacy tests and a pharmacokinetic and pharmacodynamic analysis. Thirty male crossbred Braford calves were randomly assigned to three experimental groups (n = 10), the IVM 3.15 % group (subcutaneously at 630 µg/kg), the DRM 1 % group (subcutaneously at 200 µg/kg) and the control group (saline solution subcutaneously). All treatments were performed at the time of castration surgery through a scrotal incision, and the wounds were exposed to natural infestations of C. hominivorax. Wound inspections were carried out on days 3, 6, and 13 post-treatments. Jugular blood samples were taken from experimental animals at 3- and 6-days post-treatment. In presence of C. hominivorax larvae, samples of both the larvae and wound secretions were collected in plastic vials on days 3 and 6 to measure concentrations of both drugs by high-performance liquid chromatography. On day 3 post-treatment, active myiasis was observed in 9 animals from the control group, 5 from the IVM 3.15 % group, and 6 from the DRM 1 % group. On day 6 post-treatment, 5 and 3 new myiasis were detected in the IVM 3.15 % and DRM 1 % group, respectively. No larvae were observed in the wounds on day 13 post-treatment. Interestingly, DRM concentrations tended to be higher in larvae compared to IVM on day 3 post-treatment (p = 0.051), and IVM plasma concentrations tended to be higher than those measured for DRM on day 6 (p = 0.087). There was a very strong correlation between DRM and IVM concentrations in plasma and wound secretions and larvae. The uptake of DRM from wound secretions to larvae was 83 % greater than that of IVM (p = 0.03). The results of this trial suggest the presence of C. hominivorax resistance to DRM and highlight concern about the lack of effectiveness of IVM 3.15 % in preventing C. hominivorax infestations. •IVM and DRM were detected in plasma, wound secretions, and larvae on the evaluated days.•Drug concentrations in larvae reflected those observed in plasma and wound secretions.•DRM concentration was higher in larvae than IVM on 3 days post-treatment (DPT).•DRM concentration was higher in plasma than IVM on 3 DPT, and lower on day 6 DPT.•Both drugs did not prevent C. hominivorax larvae infestation.