![]() 4 The effect of patient genetic polymorphism in relation to intestinal CYP3A4 concentration makes for an interaction that is highly difficult to predict from patient to patient regardless of the amount or concentration of grapefruit consumed. 2 Another study demonstrated that the inhibition of CYP3A4 can persist for 24 to 72 hours, 3 whereas Takanaga and colleagues have shown the interaction to persist for 72 hours. (For an extensive list of drugs affected by grapefruit juice. For example, one study has shown that intestinal CYP3A4 concentration can be decreased by 47 percent within four hours of grapefruit consumption. This enzyme breaks down a wide array of medications, including atorvastatin (Lipitor). We also feel that the evidence reported in the literature is unclear in describing the magnitude and duration of the effect of grapefruit on the intestinal cytochrome P450 3A4 (CYP3A4) isoenzyme system. Grapefruit juice inhibits the CYP3A4 enzyme of the cytochrome P450 system in the intestinal mucosa, increasing the bioavailability of drugs with a high first. This condition affects less than 0.1 of people taking statins. We are also aware of this and consequently labeled our key recommendations for practice with a SORT evidence rating of C (consensus, disease-oriented evidence, usual practice, expert opinion, or case series). Consuming grapefruit or grapefruit juice when taking statins comes with a rare but serious risk of rhabdomyolysis. Reamy and Stephens are rightly concerned about the lack of clinical and patient-oriented outcomes regarding grapefruit interactions. ![]() Even patients who enjoy grapefruit juice do not ingest more than one quart each day! Additionally, one study cited by the authors showed that when simvastatin was taken 24 hours after ingestion of the same large volume (1,200 mL) of grapefruit juice, the effect of grapefruit juice on the concentration of simvastatin was only 10 percent of that when the statin and juice were taken concomitantly. ![]() Specifically, 200 mL of double-strength juice was consumed three times per day, which equates to 1,200 mL (40 oz) per day of regular-strength grapefruit juice. Statin medications have made it possible for many people to live longer and healthier lives, but it is grapefruit interaction with atorvastatin to pay attention. The cited studies also used high-dose statins (80 mg of lovastatin, 60 mg of simvastatin) and unrealistically high volumes of grapefruit juice. Whether there is a log-linear relationship between serum concentration and clinical morbidity is a matter of debate. An additional, and perhaps more significant concern is that these studies demonstrated no clinical or patient-oriented outcomes they merely reported increased serum concentrations of lovastatin (Mevacor) and simvastatin (Zocor). ![]()
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