Concentration-dependent inhibition and activation of CYP3A4 by TRAM-34 with two substrates.

Abstract

<p>Recombinant enzyme CYP3A4, substrates DBF (A) or BFC (B) and varying concentrations of TRAM-34 were incubated in the presence of 50 mM potassium phosphate buffer and regenerating system at 37°C according to the methods described. Pmol of product (ordinate) is plotted versus the log of inhibitor concentration (abscissa) for the incubation times specified in parenthesis. All TRAM-34 data points represent the mean ±SEM of 3 experiments performed in triplicate. Data from ketoconazole represent the mean ±SEM of triplicates from a single experiment. The TRAM-34 IC₅₀ value was determined by non-linear regression and are shown in brackets (A). Control data points (i.e. no inhibitor, C on abscissa) represent the mean ±SEM from 3 experiments.</p