Effects of the multidrug-resistance-reversing agents verapamil and CL 347,099 on the efficacy of ivermectin or moxidectin against unselected and drug-selected strains of Haemonchus contortus in jirds (Meriones unguiculatus)

The development of anthelmintic resistance is making parasite control in sm all ruminants problematic. Following the discovery that the drug transporte r P-glycoprotein may be involved in macrocyclic lactone resistance in Haemo nchus contortus, we determined the effect of two multidrug-resistance modul ators, verapamil and CL347,099, on the efficacy of ivermectin and moxidecti n against unselected and drug-selected strains of H. contortus. CL347,099 i s an analog of verapamil that has multidrug-resistance properties but weake r calcium-channel-blocking activity than the parent drug. The combinations of verapamil with either ivermectin or moxidectin significantly reduced wor m counts of the selected strains as compared with the untreated controls, w hereas ivermectin or moxidectin alone did not significantly reduce worm cou nts as compared with the untreated controls. The CL347,099 plus moxidectin combination was significantly more efficacious than moxidectin alone agains t the ivermectin-selected strain. The drug-combination regimes were without adverse effect on the jirds. However, higher levels of verapamil (greater than or equal to 40 mg/kg) produced some toxicity.