PMID: 8611397Apr 1, 1996Paper

Distribution and activity of doxorubicin combined with SDZ PSC 833 in mice with P388 and P388/DOX leukaemia

British Journal of Cancer
T ColomboM D'Incalci

Abstract

SDZ PSC 833 (PSC 833) is a non-immunosuppressive analogue of cyclosporin A and is a potent modifier of P-glycoprotein (P-gp)-mediated multidrug resistance. The present study was undertaken to evaluate whether doxorubicin (DOX) pharmacokinetic and anti-tumour activity on P388- and P388/DOX-resistant leukaemia was modified by PSC 833 pretreatment. P388- or P388/DOX-bearing mice were given PSC 833 intraperitoneally 30 min before an intravenous injection of DOX. The levels of DOX were determined by a high-performance liquid chromatography method in leukaemic cells and in normal tissues (heart, lung, liver, small intestine, kidney and spleen). In all tissues, DOX concentrations were significantly increased in mice pretreated with PSC 833. The difference was greatest in P-gp-overexpressing P388/DOX cells, the DOX area under the curve being approximately seven times greater after PSC 833 and DOX than after DOX alone. In P388 cells the difference was approximately 2.5 times, as in the majority of normal tissues. As expected DOX levels in P388 cells were higher than in P388/DOX cells in mice treated with DOX alone, whereas after PSC 833 and DOX the levels of DOX were similar in the two leukaemic lines. In spite of this PSC 833 was unabl...Continue Reading

Citations

Jul 5, 2005·Expert Opinion on Investigational Drugs·F Loor
Jan 24, 2002·The Journal of Pharmacology and Experimental Therapeutics·Michael Weiss, Wonku Kang
Apr 9, 1998·Critical Reviews in Clinical Laboratory Sciences·W van de VrieA M Eggermont
Aug 1, 1997·Drug Metabolism Reviews·S Garattini
Mar 27, 2010·Journal of Veterinary Internal Medicine·D L Gustafson, D H Thamm
Oct 18, 2000·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·R Krishna, L D Mayer
Oct 3, 1999·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·E BovenO van Tellingen
Mar 3, 1998·Blood Reviews·D S Richardson, S A Johnson
Dec 19, 2006·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Silvio Garattini

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