Multidrug-resistance (mdr) of tumor cell-lines to several natural product cytotoxines (e.g. vinca alkaloids, podophyllotoxine derivatives and anthracycline derivatives) is often related to enhanced expression of transmembraneous P-glykoproteine (pgp), which is encoded in humans by the mdrl-gene. Pgp acts as an outward-flow pump (multi-drug-carrier) and lowers the intracellular concentrations of the abovementioned drugs. In vitro studies have shown that the calcium-antagonist verapamil can reverse mdr in many human or animal tumor cell-lines by blocking pgp, but in vivo reversal of drug resistance in animals could only be proved in some tumor lines. In a limited number of investigations, an impact of verapamil-coadministration on the tumor progression in patients with mdr was demonstrable for only a minor part of the treated subjects.

Keywords:
Verapamil, Multidrug-resistance, Clinical trials
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© 1991 S. Karger AG, Basel
1991
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