Can co-administered agents reduce irinotecan and capecitabine activation?
Sara K. Quinney, Daryl J. Murry and William F. Bosron Purdue University, Indianapolis, IN, University of Iowa, Iowa City, IA, Indiana University, Indianapolis, IN. Carboxylesterase enzymes are involved in the metabolism of drugs containing ester and amide constituents. The anticancer agents capecitabine and irinotecan (CPT-11) undergo in vivo activation requiring carboxylesterases. The purpose of this study was to develop a simple screening assay to identify drugs that bind to carboxylesterases in order to identify potential drug-drug interactions with capecitabine or irinotecan. Methods: Drugs commonly co-administered with irinotecan or capecitabine were evaluated. Drugs were incubated with purified human carboxylesterases, CES1 and CES2. Inhibition constants (Ki) were determined spectrophotometrically by monitoring conversion of 4-methylumbilliferyl acetate (4-MUA) to 4-methlyumbelliferone at 350 nm in the presence of varying concentrations of inhibitor and purified CES1 or CES2. The
