Grapefruit juice, inhibitory effect

Fuhr, U., Klittich, K. et al. (1993). Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man. Br. J. Clin. Pharmacol., 35(4), 431-6. 

The patients who showed some evidence of an interaction between grapefruit juice and warfarin may possibly have had an increased susceptibility to the inhibitory effects of grapefruit juice on the activity of the cytochrome P450 isoenzyme CYP3A4 in the gut. ... 

From the studies above it appears that grapefruit juice may have a minor inhibitory effect on the metabolism of omeprazole and lansoprazole by the cytochrome P450 isoenzyme CYP3A4 (which results in the sulphone metabolites). This was suggested to be due to intestinal inhibition of CYP3A4., Grapefruit juice does not affect the metabolism (hydroxyla-tion) of the proton pump inhibitors by CYP2C19. 

These predictions are as yet unconfirmed, but it would certainly be prudent to monitor sirolimus levels closely if these drugs are used concurrently. What should be remembered is that the extent of the inhibitory effects of these drugs is not identical, so that very marked effects like those observed with ketoconazole may not occur, nevertheless the interaction may still be clinically important. Grapefruit juice also inhibits CYP3A4 (potentially raising sirolimus levels), and in this case the manufacturers recommend that concurrent use should be avoided. - ... 

Fuhr U, Klittich K, Staib AH, Inhibitory effect of grapefruit juice and the active component, naringenin on CYPl A2 dependent metabolism of caffeine in man. BrJ Clin Pharmacol (1993) 35,431-6, [Title corrected by erratum],... 

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