A new and extremely rapid inducer of a cytochrome P-450-dependent monooxygenase species in rat liver microsomes.

The effect of Sulmazol, a new and extremely fast acting inducer of cytochrome P-450-dependent monooxygenase on rat liver microsomes is described. Actinomycin D prevented the induction by 60%. Despite a dramatic increase of monooxygenase activity no increase of cytochrome P-450 content could be observed. The induced P-450 species has not been identified yet; it has to possess very high specific activity, since increases of monooxygenase greater than 10-fold have been observed within 12 hours; the average increase is about 6-fold. The time course and the persistence of the induction after a single administration have been measured. Sulmazol is a strong competitive inhibitor of 7-ethoxycoumarin dealkylase activity with Ki = 1.1 muM. The main metabolite formed with microsomes of induced animals or in hepatocytes is a sulfoxidized compound rather than a hydroxylated derivative.