Regioselective oxidation of phospho-NSAIDs by human cytochrome P450 and flavin monooxygenase isoforms: implications for their pharmacokinetic properties and safety

Authors: Xie G, Wong CC, Cheng KW, Huang L, Constantinides PP, Rigas B
Publication: Br J Clin Pharmacol
Keywords: anti-inflammatory agents, biological models, cytochrome P-450 enzyme system, humans, ibuprofen, liver metabolism, non-steroidal metabolism, organophosphates, oxidation-reduction, oxygenases, recombinant proteins, sulindac
Software: ADMET Predictor®

Background and Purpose

Phospho-ibuprofen (MDC-917) and phospho-sulindac (OXT-328) are highly effective in cancer and arthritis treatment in preclinical models. Here, we investigated their metabolism by major human cytochrome P450s (CYPs) and flavin monooxygenases (FMOs).