Inhibition of human UDP-glucuronosyltransferase enzymes by lapatinib, pazopanib, regorafenib and sorafenib: Implications for hyperbilirubinemia

Autor: Nuy Chau, Kushari Burns, John O. Miners, Ross A. McKinnon, Kathleen M. Knights, Andrew Rowland, Geoffrey T. Tucker, Peter I. Mackenzie, Ganessan Kichenadasse
Rok vydání: 2017
Předmět:
Zdroj: Biochemical Pharmacology. 129:85-95
ISSN: 0006-2952
Popis: Kinase inhibitors (KIs) are a rapidly expanding class of drugs used primarily for the treatment of cancer. Data relating to the inhibition of UDP-glucuronosyltransferase (UGT) enzymes by KIs is sparse. However, lapatinib (LAP), pazopanib (PAZ), regorafenib (REG) and sorafenib (SOR) have been implicated in the development of hyperbilirubinemia in patients. This study aimed to characterise the role of UGT1A1 inhibition in hyperbilirubinemia and assess the broader potential of these drugs to perpetrate drug-drug interactions arising from UGT enzyme inhibition. Twelve recombinant human UGTs from subfamilies 1A and 2B were screened for inhibition by LAP, PAZ, REG and SOR. IC50 values for the inhibition of all UGT1A enzymes, except UGT1A3 and UGT1A4, by the four KIs were
Databáze: OpenAIRE