Ticlopidine decreases the in vivo activity of CYP2C19 as measured by omeprazole metabolism

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 w ithout ticlopidine (300 mg daily for 6 days) to six Japanese extensive meta bolisers with respect to CYP2C19. Blood samples were taken for the measurem ent of plasma concentrations of omeprazole, 5-hydroxyomeprazole and omepraz ole sulphone. Results Ticlopidine administration increased omeprazole C-max (1978+/-859/3 442+569 (control phase/ticlopidine phase, nM)) and decreased the oral clear ance of omeprazole (CL/F; 25.70 +/- 16.17/10.76 +/- 1.16 (control phase/tic lopidine phase, 1h(-1))) significantly. The 5-hydroxyomeprazole to omeprazo le AUC ratio (0.817 +/- 0.448/0.236 +/- 0.053 (control phase/ticlopidine ph ase)) and the 5-hydroxyomeprazole to omeprazole sulphone AUC ratio (1.114+/ -0.782/0.256+/-0.051 (control phase/ticlopidine phase)) were decreased sign ificantly after ticlopidine administration. The decrease in omeprazole CL/F and the 5-hydroxyomeprazole to omeprazole AUC ratio correlated significant ly 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 a ctivity of CYP2C19, but not, or to a lesser extent CYP3 A4: and that the ma gnitude of inhibition by ticlopidine is related to the in vivo activity of CYP2C19 before inhibition.