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) |
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Authors: | Marcelo B Molento Roger K Prichard |
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Institution: | (1) Institute of Parasitology, McGill University, 21,111 Lakeshore Road, Sainte Anne-de-Bellevue, Quebec H9X 3V9, Canada e-mail: rprichar@parasit.lan.mcgill.ca Tel: +1-514-3987729; Fax: +1-514-3987857, CA |
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Abstract: | The development of anthelmintic resistance is making parasite control in small ruminants problematic. Following the discovery
that the drug transporter P-glycoprotein may be involved in macrocyclic lactone resistance in Haemonchus contortus, we determined the effect of two multidrug-resistance modulators, verapamil and CL347,099, on the efficacy of ivermectin
and moxidectin against unselected and drug-selected strains of H. contortus. CL347,099 is an analog of verapamil that has multidrug-resistance properties but weaker calcium-channel-blocking activity
than the parent drug. The combinations of verapamil with either ivermectin or moxidectin significantly reduced worm counts
of the selected strains as compared with the untreated controls, whereas ivermectin or moxidectin alone did not significantly
reduce worm counts as compared with the untreated controls. The CL347,099 plus moxidectin combination was significantly more
efficacious than moxidectin alone against the ivermectin-selected strain. The drug-combination regimes were without adverse
effect on the jirds. However, higher levels of verapamil (≥40 mg/kg) produced some toxicity.
Received: 26 March 1999 / Accepted: 30 July 1999 |
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