OMEPRAZOLE AND LANSOPRAZOLE ARE MIXED INDUCERS OF CYP1A AND CYP3A IN HUMAN HEPATOCYTES IN PRIMARY CULTURE

The ability of several gastric antiulcer drugs including lansoprazole, cimetidine and ranitidine to affect the expression of human liver mic rosomal cytochromes P450 comparatively to omeprazole, reported previou sly to be a CYP1A inducer, was evaluated in primary cultures of human hepatocytes. Poly (A)(+) RNA and microsomes extracted from the cells w ere analyzed in Northern and Western blots with specific cDNA probes a nd antibodies, and assayed for form-specific monoxygenase activities. Lansoprazole induced both CYP1A1 and CYP1A2 as omeprazole and did not apparently bind to the aryl hydrocarbon receptor with high affinity. O meprazole sulfone was not an inducer of CYP1A. Omeprazole, omeprazole sulfone and lansoprazole induced CYP3A in approximately 50% of tested cultures, whereas 100% of tested cultures responded to omeprazole and to rifampicin in terms of CYP1A and CYP3A induction, respectively. Fin ally, cimetidine and ranitidine were not inducers. We conclude that om eprazole and lansoprazole constitute a new class of mixed inducers of CYP1A and CYP3A in human hepatocytes in primary culture and that the i nduction of CYP3A in response to these molecules could be polymorphic in humans.