Role of hepatic transporters in the disposition and hepatotoxicity of a HER2 tyrosine kinase inhibitor CP-724,714.
AuthorsFeng B, Xu JJ, Bi YA, Mireles R, Davidson R, Duignan DB, Campbell S, Kostrubsky VE, Dunn MC, Smith AR, Wang HF,
JournalToxicol Sci
PubMed ID19223659
'CP-724,714, a potent and selective orally active HER2 tyrosine kinase inhibitor, was discontinued from clinical development due to unexpected hepatotoxicity in cancer patients. Based on the clinical manifestation of the toxicity, CP-724,714 likely exerted its hepatotoxicity via both hepatocellular injury and hepatobiliary cholestatic mechanisms. The direct cytotoxic effect, hepatobiliary disposition ... More