Formation of omeprazole sulphone but not 5-hydroxyomeprazole is inhibited by grapefruit juice

Aims To determine the effect of grapefruit juice on omeprazole metabolism i n vivo. Methods This was a randomized crossover study with a 2 week washout period. Omeprazole (20 mg) was taken orally by 13 healthy volunteers after an over night fast with either grapefruit juice or water. Serial blood samples were obtained over 12 h and standardized meals were served 3 and 10 h after the administration of omeprazole. Plasma concentrations of omeprazole and its major metabolites, 5-hydroxyomeprazole and omeprazole sulphone, were determ ined by high performance liquid chromatography (h.p.l.c.). Results Mean area under the plasma concentration vs time curve (AUC) betwee n 0 and 12 h for omeprazole sulphone was approximately 20% lower (P<0.01) i n the group receiving grapefruit juice. There was no significant difference in the mean AUC of 5-hydroxyomeprazole or omeprazole. The AUC ratio of ome prazole sulphone to omeprazole, an index of CYP3A4 activity, was decreased by 33% (P<0.001) after administration of grapefruit juice whereas the AUC r atio of 5-hydroxyomeprazole to omeprazole, an index of CYP2C19 activity, di d not differ between the two phases of the study. Although the time to peak concentration (t(max)) and terminal half-life (t(1/2,z)) Of omeprazole and its two main metabolites were not altered, the peak concentration (C-max) of omeprazole sulphone was significantly reduced after administration of gr apefruit juice. Conclusion Administration of grapefruit juice decreased che formation or om eprazole sulphone but not 5-hydroxyomeprazole. These results indicate that activities of CYP3A4, but not of CYP2C19, are inhibited by the simultaneous administration of grapefruit juice.