Grapefruit juice reduced the peak plasma concentration of the active metabolite of clopidogrel to 13% of the control (P<0.001), impairing its efficacy.
RCT (n=14)
crossover
Does grapefruit juice reduce the metabolic activation of clopidogrel in healthy volunteers?
Concomitant use of grapefruit juice significantly impairs the metabolic activation and efficacy of clopidogrel, suggesting it should be avoided during therapy.
p-value: p=<0.001
Cytochrome P450 (CYP) enzymes, including CYP2C19 and CYP3A4, participate in the bioactivation of clopidogrel. Grapefruit juice constituents potently inactivate intestinal CYP3A4 and have been shown to inhibit CYP2C19 as well. In a randomized crossover study, 14 healthy volunteers ingested 200 ml of grapefruit juice or water three times daily for 3 days. On day 3, they ingested a single 600-mg dose of clopidogrel. Grapefruit juice reduced the peak plasma concentration (Cmax) of the active metabolite of clopidogrel to 13% of the control (range 11-17%, P < 0.001) and the area under the plasma concentration-time curve from 0 to 3 h to 14% (range 12-17%, P < 0.001) of the control, but it had no significant effect on the parent clopidogrel. Moreover, grapefruit juice markedly decreased the platelet-inhibitory effect of clopidogrel, as assessed with the VerifyNow P2Y12 test in two of the participants. In conclusion, concomitant use of grapefruit juice may impair the efficacy of clopidogrel. Therefore, the use of grapefruit juice is best avoided during clopidogrel therapy.
Holmberg et al. (Wed,) conducted a rct in healthy volunteers (n=14). Grapefruit juice vs. Water was evaluated on peak plasma concentration (Cmax) of the active metabolite of clopidogrel (p=<0.001). Grapefruit juice reduced the peak plasma concentration of the active metabolite of clopidogrel to 13% of the control (P<0.001), impairing its efficacy.