Inhibition of the sulfoxidation of omeprazole by ketoconazole in poor and extensive metabolizers of S-mephenytoin*

Abstract

An oral daily dose of 100 to 200 mg ketoconazole is sufficient to provide a marked inhibition of the formation of the omeprazole sulfone in both extensive and poor metabolizers and leads to a doubling of omeprazole levels in poor metabolizers, whereas 50 mg ketoconazole provides only partial inhibition. We concluded that CYP3A4 catalyzes the sulfoxidation of omeprazole and that this is the predominant metabolic pathway of omeprazole in poor metabolizers of S-mephenytoin.