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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Adolescent, Adult, Aged, Antineoplastic Agents, Phytogenic, Area Under Curve, Camptothecin, Drug Interactions, Female, Glucuronides, Glucuronosyltransferase, Humans, Irinotecan, Male, Microsomes, Liver, Middle Aged, Protein Kinase Inhibitors, Pyrimidines, Young Adult.
user
Is the small-molecule tyrosine kinase inhibitor nilotinib a potent noncompetitive inhibitor of the SN-38 glucuronidation by human UGT1A1? Context: Inhibition of the UDP-glucuronosyltransferase (UGT) 1A1 by nilotinib was examined in vitro with SN-38 as a substrate, to estimate the possibility of drug-drug interaction of nilotinib with other medicines predominantly detoxified by UGT1A1. Inhibition of UGT1A1-catalyzed SN-38 glucuronidation by nilotinib was examined with human liver microsomes (HLM) and recombinant human UGT1A1 as enzyme sources. Inhibition constants (K(i)) were estimated with kinetic analysis. Nilotinib potently inhibited the SN-38 glucuronidation by human liver microsomal UGT1A1 and recombinant UGT1A1 in a noncompetitive manner, with K(i) values of 0.286 ± 0.0094 and 0.079 ± 0.0029 μM, respectively. If a drug that serves as a substrate of UGT1A1 is administered with nilotinib, the area under the plasma concentration-time curve of a drug estimated by using these K(i) values would be two times or higher than that without nilotinib, suggesting drug-drug interactions involving UGT1A1. These in vitro data and the prediction of drug-drug interaction are helpful for the clinical management of the nilotinib use.
assistant
We found that nilotinib is a potent noncompetitive inhibitor of human UGT1A1 activity. Final Decision: yes