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Influence of fluconazole on the pharmacokinetics of omeprazole in healthy volunteers
Author(s) -
Kang Byoung C.,
Yang Chang Q.,
Cho Hae K.,
Suh Ok K.,
Shin Wan G.
Publication year - 2002
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.291
Subject(s) - omeprazole , fluconazole , pharmacokinetics , cyp2c19 , cyp3a4 , pharmacology , oral administration , proton pump inhibitor , chemistry , medicine , metabolism , cytochrome p450 , antifungal , biochemistry , dermatology
Influence of fluconazole on the pharmacokinetics of omeprazole was evaluated by single oral administration of omeprazole capsule 20 mg (control group), or single oral administration of fluconazole capsule, 100 mg, and omeprazole, 20 mg, after 4 days of daily oral administration of fluconazole, 100 mg (treated group), to 18 healthy male volunteers. Omeprazole is extensively metabolized in the liver through 5‐hydroxylation and sulfoxidation reactions catalyzed predominantly by CYP2C19 and CYP3A4, respectively. Fluconazole is a potent competitive inhibitor of CYP2C19 and a weak inhibitor of CYP3A4. In treated group, the area under the plasma concentration–time curve of omeprazole from time zero to time infinity (AUC) was significantly greater (3090 vs 491 ng h/ml), terminal half‐life of omeprazole was significantly longer (2.59 vs 0.85 h), and peak plasma concentration of omeprazole ( C max ) was significantly higher (746 vs 311 ng/ml) than that in control group. The greater AUC and higher C max in treated group could be due to inhibition of omeprazole metabolism by fluconazole. Copyright © 2002 John Wiley & Sons, Ltd.