DECREASED BIOTOLERABILITY FOR IVERMECTIN AND CYCLOSPORINE-A IN MICE EXPOSED TO POTENT P-GLYCOPROTEIN INHIBITORS

SDZ PSC 833 or SDZ 280-446 are strong blockers of the function of clas s I mdr gene-encoded P-glycoprotein molecules, which were developed fo r the reversal of multi-drug-resistance of tumor cells. When treated w ith such drugs, normal mice may display hypersensitivity to cyclospori n A and ivermectin. The recorded signs of acute toxicity are compatibl e with alterations of the murine central nervous system functions and with earlier data suggesting that P-glycoprotein expressed at the muri ne blood-brain barrier might be involved in the exclusion of cyclospor in A or ivermectin from brain tissue. (C) 1995 Wiley-Liss, Inc.