Journal article
Preclinical Toxicokinetic Evaluation of Phortress [2-(4-Amino-3-Methylphenyl)-5-Fluorobenzothiazole Lysylamide Dihydrochloride] in Two Rodent Species
TD Bradshaw, JE Wren, M Bruce, DA Barrett, C-O Leong, M Gaskell, EK Wright, PB Farmer, CJ Henderson, R Wolf, MFG Stevens
PHARMACOLOGY | KARGER | Published : 2009
DOI: 10.1159/000183846
Abstract
BACKGROUND AND AIMS: The 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole prodrug Phortress exerts potent and selective antitumour activity in vitro and in vivo. Preclinical toxicokinetic studies in 2 rodent species were undertaken to determine Phortress' maximum tolerated dose and advise a safe starting dose for clinical evaluation. METHODS: Plasma pharmacokinetic parameters were determined by high-performance liquid chromatography and fluorescence detection following Phortress administration to mice (10 mg/kg, intravenously on days 1 and 8). Phortress (20 mg/kg, on days 1 and 8) was administered to CYP1A1/betaGAL reporter mice; tissues were examined macro- and microscopically. Toxicologica..
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Funding Acknowledgements
The authors would like to acknowledge collaborations with the NCI and the Drug Discovery Committee of the EORTC PAMM group, and are grateful to CR UK for financial and academic support. This paper, part 30 in the series 'Antitumour 2-(4-aminophenyl) benzothiazoles', is dedicated to Donald Bradshaw.