Decreased biotolerability for ivermectin and cyclosporin A in mice exposed to potent P-glycoprotein inhibitors.
SDZ PSC 833 or SDZ 280-446 are strong blockers of the function of class I 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.
Didier
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Immunology Laboratory, Strasbourg 1 University, Illkirch, France.
Loor
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D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000818:Animals; D001812:Blood-Brain Barrier; D016572:Cyclosporine / Q000008:administration & dosage*; D003524:Cyclosporins / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D004361:Drug Tolerance; D006824:Hybridization, Genetic; D007559:Ivermectin / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010456:Peptides, Cyclic / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003524:Cyclosporins; D010456:Peptides, Cyclic; C072534:SDZ 280 446; D007559:Ivermectin; D016572:Cyclosporine; C070272:valspodar