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Wiley, British Journal of Pharmacology, 6(130), p. 1241-1246, 2000

DOI: 10.1038/sj.bjp.0703427

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Effect of cytochrome P-450 inhibitors econazole, bifonazole and clotrimazole on prostanoid formation

Journal article published in 2000 by Harald C. Köfeler ORCID, Günter Fauler, Werner Windischhofer, Hans J. Leis
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

The present study was carried out to clarify the effect of the imidazole antimycotics econazole, bifonazole and clotrimazole on prostanoid biosynthesis. Osteoblast-like MC3T3-E1 cells stimulated by endothelin-1, melittin, ionomycin or arachidonic acid showed diminished prostaglandin E2 (PGE2) production upon pretreatment with econazole. Following pretreatment with bifonazole, stimulation with ionomycin or arachidonic acid also resulted in decreased PGE2 formation. Clotrimazole inhibited ionomycin but not arachidonic acid stimulated PGE2 synthesis in MC3T3-E1 cells.The results observed in osteoblast-like UMR-106 cells pretreated with econazole, bifonazole or clotrimazole and stimulated by arachidonic acid were similar with the exception of clotrimazole which was a more effective inhibitor of PGE2 biosynthesis than in MC3T3-E1 cells.Upon treatment with arachidonic acid thromboxane B2 (TXB2) production in human platelets was abolished completely at concentrations of the three imidazole antimycotics higher than 5 μM (IC50