Decreased biotolerability for ivermectin and cyclosporin a in mice exposed to potent P‐glycoprotein inhibitors

Abstract

SDZ PSC 833 or SDZ 280-446 are strong blockers of the function of class 1 mdr gene-encoded P-glycoprotein molecules, which were developed for the reversal of multi-drug-resistance of tumor cells. When treated with such drugs, normal mice may display hypersensitivity to cyclosporin A and ivermectin. The recorded signs of acute toxicity are compatible with alterations of the murine central nervous system functions and with earlier data suggesting that P-glycoprotein expressed at the murine blood-brain barrier might be involved in the exclusion of cyclosporin A or ivermectin from brain tissue.