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 fr equently and the concomitantly used drugs may alter the pharmacokinetics of each other. One reason for the alteration of pharmacokinetics may be the m odulation of the function of P-glycoprotein, whose efflux pump occurs in re sistant cancer cells, in human intestine and in the blood-brain barrier. Fo r this reason we tested the effect of several anti-psychotic drugs on the m ultidrug-resistant pump, P-glycoprotein. We found that in the MDR gene tran sfected L121C MDR, L5178 MDR and in the KB-V-1 cells selected for resistanc e some antipsychotic drugs block the function of P-glycoprotein. Blood cell s of two treatment-resistant leukemic patients also showed increased uptake of daunorubicin if treated ex vivo with the anti-psychotic drugs. Our resu lts suggest that pharmacokinetic studies should be performed prior to conco mitant clinical use of such drugs which block P-glycoprotein function. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.