Recombinant interleukin-2 treatment decreases P-glycoprotein activity and paclitaxel metabolism in mice

Anti-cancer Drugs
Laurence Bonhomme-FaivreRobert Farinotti

Abstract

Recombinant rIL-2 was reported to be able to decrease P-glycoprotein (P-gp) expression in cultured cells from human colon carcinoma. P-gp is considered an important factor in the control of Taxol efflux from tumor cells. Based on the premise that Taxol pharmacokinetic parameters could be modified as a result of diminished P-gp expression induced by recombinant interleukin (rIL)-2 and that this might elicit an interaction between the two drugs, we evaluated the pharmacokinetics of a novel strategy combining i.p. immunotherapy with rIL-2 and a cytotoxic agent, Taxol. Mice were allocated to two groups treated with rIL-2 (15 microg x 2/day from day 1 to 4) then Taxol (10 mg/kg i.p. day 5) or Taxol (10 mg/kg i.p.) alone (control group). The Taxol + rIL-2 combination provoked the development of ascites, presumably due to the presence of Cremophor EL in the Taxol preparation. Paclitaxel was measured in plasma and ascites by HPLC with UV detection. Paclitaxel pharmacokinetics were strongly modified by rIL-2 pretreatment. Compared to that observed in control mice, the apparent volume of distribution increased dramatically (Vd/F = 18.2 versus 4.1 l/kg) and the apparent plasma clearance decreased (Cl/F = 1.12 versus 1.66 l/h/kg). P-gp exp...Continue Reading

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Citations

Sep 21, 2004·Cancer Chemotherapy and Pharmacology·Candice JamoisLaurence Bonhomme-Faivre
Jun 1, 2012·Drug Delivery and Translational Research·William A Banks
Jul 26, 2006·Expert Opinion on Drug Metabolism & Toxicology·Kenneth W Renton
Apr 28, 2009·Progress in Neurobiology·Ivona BrasnjevicUNKNOWN European NanoBioPharmaceutics Research Initiative
Mar 3, 2007·The Journal of Pharmacy and Pharmacology·Makrem Ben ReguigaRobert Farinotti
Aug 28, 2002·The Journal of Pharmacy and Pharmacology·Anne-Marie BelliardChristine Leroy
Jan 25, 2005·Drug Metabolism and Drug Interactions·Chadi AbbaraLaurence Bonhomme-Faivre
May 30, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Benoît HostenLaurence Bonhomme-Faivre

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