Proposals for concomitant use of several modulators of multidrug resistance in clinics.
Numerous modulators of multidrug resistance present a good in vitro activity which has not always been reproduced in vivo or in clinics. One reason is the fact that the plasma concentration required might exceed the maximum tolerated dose of modulator, due to its own toxicity. In addition, it has been suggested that the different modulators thus far identified might act on different sites of P-glycoprotein and eventually on different targets. It has been shown that the combination of verapamil and quinine, and of verapamil and cyclosporine A, behave synergistically in the circumvention of multidrug resistance. There is therefore a good rationale for the evaluation of protocols combining two different modulators to cytotoxic chemotherapy.
Robert
J
J
Fondation Bergonié, Bordeaux, France.
D016572:Cyclosporine / Q000627:therapeutic use; D018432:Drug Resistance, Multiple; D004357:Drug Synergism; D005990:Glycerol / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D011803:Quinine / Q000627:therapeutic use; D014700:Verapamil / Q000627:therapeutic use
C000515:cremophor EL; D016572:Cyclosporine; D011803:Quinine; D014700:Verapamil; D005990:Glycerol