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

LIFSCHITZ A.; LLOBERAS M.; ENTROCASSO C. ; ALVAREZ LI; BALLENT M.; VIRKEL G.; MATÉ L.; LANUSSE C.

Buenos Aires

Conferencia; 23rd. International Conference of the World Association for the Advancement of Veterinary Parasitology (WAAVP); 2011

World Association for the Advancement of Veterinary Parasitology (WAAVP)

Abamectin (ABM), ivermectin (IVM) (avermectins) and moxidectin (MXD) (milbemycin) are close related broad-spectrum endectocide compounds. However, differential efficacy patterns against resistant nematodes have been reported, which may be based on specific pharmacokinetic/pharmacodynamic features of each molecule. This work aimed to measure the comparative concentration profiles of ABM, IVM and MXD achieved in the bloodstream, the gastrointestinal contents/tissues and within 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 H. contortus exposed to the three compounds was established. Thirty (30) naturally parasitized lambs were assigned into three experimental groups intraruminally treated with either ABM, IVM or 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 the 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 compared to that of both ABM and IVM. Concentrations of IVM obtained in abomasal content (day 2 post-treatment) were higher 125 ng/g) compared to that measured after MXD treatment (32 ng/g). There was a positive correlation between drug concentrations measured in abosamal content and those recovered in H. contortus collected from treated lambs. However, higher concentrations of ABM (146 ng/g), IVM (238 ng/g) and MXD (60 ng/g) were measured within 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 within resistant H. contortus specimens tended to be lower than those of 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.