PRODUCT INHIBITION OF AMINOPYRINE N-DEMETHYLATION IN ISOLATED HEPATOCYTES

Abstract

The product inhibition of aminopyrine (AM) N-demethylation by 4-monomethylaminoantipyrine (MAA) was examined in vitro in preparations of isolated rat hepatocytes using gas chromatograph-mass spectrometer (GC-MS). the kinetic study of AM N-demethylation, which was determined by MAA formation, was studied at concentrations from 0.2 to 4.0 mM with or without various concentrations of D₃-MAA.D₃-MAA inhibited AM N-demethylation non-competitively at concentrations of 0.2 to 1.0 mM of AM (k_i=1.81 m_M), though it did competitively at concentations of 1.0 to 4.0 mM of AM (K_i=0.81 mM). From the present observation, it was suggested that the inhibition type of AM N-demethylation by D₃-MAA was dependent on the substrate (AM) concentration.