Improved oral bioavailability in rats of SR13668, a novel anti-cancer agent.

Cancer Chemotherapy and Pharmacology
Carol GreenIzet M Kapetanovic

Abstract

SR13668, a bis-indole with potent activity in vitro and in vivo against various cancers and promising cancer chemopreventive activity, was found to have very low oral bioavailability, <1%, in rats during pilot pharmacokinetic studies. The objective of these studies was to better understand the source of low oral exposure and to develop a formulation that could be used in preclinical development studies. An automated screening system for determining solubility in lipid-based vehicles, singly and in combination, was used to identify formulations that might enhance absorption by improving solubility of SR13668, and these results were confirmed in vivo using Sprague-Dawley rats. Pharmacokinetics of SR13668 was then determined in male and female Sprague-Dawley rats administered 1 mg/kg iv, 1, 10, and 30 mg/kg po formulated in PEG400:Labrasol (1:1 v/v). Blood was collected at time points through 24 h and the concentration of SR13668 determined using HPLC with UV and fluorescence detection. SR13668 was found to be resistant to plasma esterases in vitro and relatively stable to rat and human liver microsomal metabolism. SR13668 concentrates in tissues as indicated by significantly higher levels in lung compared to blood, blood concentr...Continue Reading

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Citations

Mar 5, 2011·Cancer Prevention Research·Joel M ReidUNKNOWN Cancer Prevention Network
Sep 12, 2017·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Jiake HeYang Lu
Sep 8, 2018·Chemical Reviews·Tomasz JanosikJan Bergman

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