PMID: 9446255Jan 31, 1998Paper

SDZ PSC 833: a novel modulator of MDR

Tumori
A Covelli

Abstract

SDZ PSC 833 is a novel compound able to reverse the resistance to chemotherapy of cancer cells with the multidrug resistance (MDR) phenotype by inhibiting the 170 kd P-glyco-protein (P-gp). In vitro studies show that SDZ PSC 833 directly interacts with, but is not transported by P-gp, although the exact mechanism of action has not yet been defined. In cells with the MDR phenotype, intracellular concentration of various P-gp-transported anticancer drugs is restored to the same level as in sensitive cells by SDZ PSC 833 concentrations of 0.8 microM to 3.0 microM. In vivo SDZ PSC 833 was highly active in potentiating the anti-tumour activity of all tested anticancer drugs (ACs) in both sensitive and MDR tumours. Sensitivity of non-MDR tumours was increased by SDZ PSC 833 through pharmacokinetic interactions, that result in enhanced area-under-the-curve (AUC) of P-gp-transported ACs. However, an increased AC bioavailability is not sufficient to explain the therapeutic benefit of SDZ PSC 833 co-treatment in MDR tumour-bearing mice: in these animals, no survival increase could be achieved with the AC alone by simply increasing the cytotoxin dosage up to doses that were severely toxic for the non-tumour-bearing mice. In a series of ph...Continue Reading

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