Effect of the multidrug resistance modulator valspodar on serum cortisol levels in rabbits

Cancer Chemotherapy and Pharmacology
T CuferBranimir I Sikic

Abstract

To contribute to a better understanding of the physiological role of P-glycoprotein (P-gp) in the adrenal gland, we initiated our studies in rabbits. The aim of our study was to explore the effect of the selective multidrug resistance (MDR) modulator PSC 833 (valspodar) on serum cortisol in rabbits. Baseline and corticotropin-stimulated serum cortisol levels were measured before and after valspodar treatment in adult male rabbits. Seven rabbits were treated with 50 mg/kg per dose and seven, with 75 mg/kg per dose of valspodar subcutaneously. Serum cortisol levels were determined by radioimmunoassay adjusted for expected values. Serum cortisol levels (baseline as well as corticotropin-stimulated) increased after both valspodar treatment regimens. The increase was dose-dependent and was higher for the baseline than for the corticotropin-stimulated values. Serum valspodar levels exceeding 1000 ng/ml were achieved in all except one animal in each group. We hypothesize that the increased serum cortisol levels were due to increased adrenocorticotropic hormone (ACTH) secretion after valspodar treatment, but, unfortunately, we could not measure ACTH properly in rabbits by means of the commercially available kits. Our study indicates th...Continue Reading

Citations

Jul 5, 2005·Expert Opinion on Investigational Drugs·F Loor
Apr 6, 2006·Liver International : Official Journal of the International Association for the Study of the Liver·Karin DilgerUlrich Beuers
Jan 2, 2014·Toxicology and Applied Pharmacology·Elisabeth FilipskiAlper Okyar
Nov 12, 2009·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Z BinkhathlanA Lavasanifar

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