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Journal of Pharmacology and Experimental Therapeutics

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Abstract

Omeprazole and lansoprazole are mixed inducers of CYP1A and CYP3A in human hepatocytes in primary culture.

R Curi-Pedrosa, M Daujat, L Pichard, J C Ourlin, P Clair, L Gervot, P Lesca, J Domergue, H Joyeux and G Fourtanier
Journal of Pharmacology and Experimental Therapeutics April 1994, 269 (1) 384-392;
R Curi-Pedrosa
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M Daujat
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L Pichard
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J C Ourlin
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P Clair
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L Gervot
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P Lesca
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J Domergue
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H Joyeux
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G Fourtanier
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Abstract

The ability of several gastric antiulcer drugs including lansoprazole, cimetidine and ranitidine to affect the expression of human liver microsomal cytochromes P450 comparatively to omeprazole, reported previously to be a CYP1A inducer, was evaluated in primary cultures of human hepatocytes. Poly (A)+ RNA and microsomes extracted from the cells were analyzed in Northern and Western blots with specific cDNA probes and 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. Omeprazole 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. Finally, cimetidine and ranitidine were not inducers. We conclude that omeprazole and lansoprazole constitute a new class of mixed inducers of CYP1A and CYP3A in human hepatocytes in primary culture and that the induction of CYP3A in response to these molecules could be polymorphic in humans.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 269, Issue 1
1 Apr 1994
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Abstract

Omeprazole and lansoprazole are mixed inducers of CYP1A and CYP3A in human hepatocytes in primary culture.

R Curi-Pedrosa, M Daujat, L Pichard, J C Ourlin, P Clair, L Gervot, P Lesca, J Domergue, H Joyeux and G Fourtanier
Journal of Pharmacology and Experimental Therapeutics April 1, 1994, 269 (1) 384-392;

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Abstract

Omeprazole and lansoprazole are mixed inducers of CYP1A and CYP3A in human hepatocytes in primary culture.

R Curi-Pedrosa, M Daujat, L Pichard, J C Ourlin, P Clair, L Gervot, P Lesca, J Domergue, H Joyeux and G Fourtanier
Journal of Pharmacology and Experimental Therapeutics April 1, 1994, 269 (1) 384-392;
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