Anti-psychotic drugs reverse multidrug resistance of tumor cell lines and human AML cells ex-vivo.
Anti-psychotic drugs are used in cancer patients undergoing chemotherapy frequently and the concomitantly used drugs may alter the pharmacokinetics of each other. One reason for the alteration of pharmacokinetics may be the modulation of the function of P-glycoprotein, whose efflux pump occurs in resistant cancer cells, in human intestine and in the blood-brain barrier. For this reason we tested the effect of several anti-psychotic drugs on the multidrug-resistant pump, P-glycoprotein. We found that in the MDR gene transfected L121C MDR, L5178 MDR and in the KB-V-1 cells selected for resistance some antipsychotic drugs block the function of P-glycoprotein. Blood cells of two treatment-resistant leukemic patients also showed increased uptake of daunorubicin if treated ex vivo with the anti-psychotic drugs. Our results suggest that pharmacokinetic studies should be performed prior to concomitant clinical use of such drugs which block P-glycoprotein function.
Institute of Microbiology, Albert Szent-Györgyi Medical University, Szeged, Hungary.
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Szabó
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Szabó
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Ocsovszki
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Aszalos
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Molnár
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D014150:Antipsychotic Agents / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology; D003630:Daunorubicin / Q000493:pharmacokinetics; D004347:Drug Interactions; D018432:Drug Resistance, Multiple; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D020112:Rhodamine 123 / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014150:Antipsychotic Agents; D004791:Enzyme Inhibitors; D020112:Rhodamine 123; D016572:Cyclosporine; D003630:Daunorubicin