The p-glycoprotein inhibitor ketoconazole causes a reversion to sensitivity in ivermectin resistant cyathostomins in vitro

Anthelmintic resistance is a growing problem in both the developed and developing world; of most concern is the level of resistance detected against the potent macrocylic lactone (ML) anthelmintics. To identify and target a common mechanism of resistance to anthelmintics would allow potential modification of existing drugs, and may even enable the prediction and prevention of the development of resistance to novel drugs. There is a growing body of evidence that P-glycoproteins (P-gps) are involved in resistance to the MLs in many parasitic nematodes of humans and veterinary species (Ardelli et al, 2011). P-gps belong to class two of the ATP binding cassette (ABC) transporter protein superfamily; they are responsible for the active removal of xenobiotic compounds from cells. The cyathostomins are gastrointestinal nematodes of equids that cause significant pathology. Recently resistance to MLs has been described in cyathostomins (Molento et al, 2008), its mechanisms have not yet been elucidated.