Comparative measurement of abamectin, ivermectin and moxidectin concentrations in resistant Haemonchus contortus

Abstract

Abamectin (ABM), ivermectin (IVM) (avermectins) and moxidectin (MXD) (milbemycin) are close related broadspectrum endectocide cpmpounds. However, differencial efficacy patterns against resistant nematodes have been reported, wich may be based on specific pharmacokinetic/pharmacodynamic features of each molecule. This work aimed to measure the comparative concentration of ABM, IVM and MXD achieved in the bloodstream, the gastrointestinal contents/tissues and whithin a target abomasal parasite (H. contortus) in lambs naturally infected with resistant nematodes. Additionally, the pattern of the drug-transporter P-glycoprotein (P-gp) mRNA expression in the H. contortus exposed to the three compounds was established. Thirty (30) naturally parasitized lambs were assigned into three experimental groups intraruminally treated with ABM, IVM and MXD at 0.2 mg/kg. Blood samples were collected from six animals in each treated group over 14 days post-treatment. Four animals from each group were sacrificed at day 2 post-treatment. Mucosal and fluid content samples from abomasum and small intestine were collected. Adult specimens of H. contortus were recovered from the abomasum. Drug concentrations were measured by HPLC. Specific P-gp mRNA levels in H contortus were quantified by real time PCR. A similar plasma systemic exposure (AUC values) was obtained for the endectocide molecules. However MXD persistence in the bloodstream was longer (P<0.05) compared to that of both ABM and IVM. Concentrations of IVM obteined in abosamal content (2 day post-treatment) were higher (P<0.05) (125 ng/g) compared to that measured after MXD treatment (32 ng/g). There was a positive correlation between drug concentrations measured in abomasal content and those in H. contortus collected from treated lambs. Hoowever, higher concentrations of ABM (146 ng/g), IVM (238 ng/g) and MXD (60 ng/g) were measured whithin H.contortus compared to those observed in plasma and abomasal content. No significant differences on P-gp expression were observed in H. contortus specimens in vivo exposed to the different drugs. Although MXD concentrations recovered at target tissues and whithin resistant H. contortus specimens tended to be lower than those IVM and ABM, some differential pharmacodynamic features may have accounted for the advantageous efficacy pattern against the same resistant H. contortus strain observed in a parallel trial.