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Ticlopidine decreases the in vivo activity of CYP2C19 as measured by omeprazole metabolism
Author(s) -
Tateishi Tomonori,
Kumai Toshio,
Watanabe Minoru,
Nakura Hironori,
Tanaka Masami,
Kobayashi Shinichi
Publication year - 1999
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.1999.00914.x
Subject(s) - omeprazole , ticlopidine , cyp2c19 , pharmacology , in vivo , pharmacokinetics , chemistry , oral administration , medicine , metabolism , cytochrome p450 , clopidogrel , biology , aspirin , microbiology and biotechnology
Aims To examine the effect of ticlopidine administration on the activities CYP2C19 and CYP3 A in vivo using omeprazole as a model substrate. Methods A single dose of 40 mg omeprazole was administered orally with or without ticlopidine (300 mg daily for 6 days) to six Japanese extensive metabolisers with respect to CYP2C19. Blood samples were taken for the measurement of plasma concentrations of omeprazole, 5‐hydroxyomeprazole and omeprazole sulphone. Results Ticlopidine administration increased omeprazole C max (1978±859/ 3442±569 (control phase/ticlopidine phase, nm )) and decreased the oral clearance of omeprazole (CL/F; 25.70±16.17/10.76±1.16 (control phase/ticlopidine phase, l h −1 )) significantly. The 5‐hydroxyomeprazole to omeprazole AUC ratio (0.817±0.448/0.236±0.053 (control phase/ticlopidine phase)) and the 5‐hydroxyomeprazole to omeprazole sulphone AUC ratio (1.114±0.782/0.256±0.051 (control phase/ticlopidine phase)) were decreased significantly after ticlopidine administration. The decrease in omeprazole CL/F and the 5‐hydroxyomeprazole to omeprazole AUC ratio correlated significantly with their respective absolute values when the drug was given alone. The decrease in CL/F following ticlopidine administration correlated with that in the 5‐hydroxyomeprazole to omeprazole AUC ratio. Conclusions These findings suggest that ticlopidine inhibited the in vivo activity of CYP2C19, but not, or to a lesser extent CYP3 A4, and that the magnitude of inhibition by ticlopidine is related to the in vivo activity of CYP2C19 before inhibition.