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DRUG INTERACTIONS

DRUG INTERACTIONS

There are no known specific drug interactions for POM Wonderful PJ. As noted in the Clinical Overview on page 11, the juice has been given to type 2 diabetics taking oral hypoglycemic drugs for 3 months with no apparent negative effects on glycemic control.10

Due to reports of grapefruit juice’s inhibiting cytochrome P450 isoenzymes and subsequent hepatic and enteric (within the intestine) drug metabolism,124 there has been concern about the potential for drug interactions with other commercial fruit juices including PJ. A case report of a 48 year-old man developing rhabdomyolysis while taking rosuvastatin (5 mg every other day) and PJ (200 ml twice weekly) concomitantly, has also drawn focus to this concern for PJ.125 It should be noted that the link between PJ and development of rhabdomyolysis is quite weak in this case because the subject had increased creatine kinase levels while not taking medication and because rosuvastatin is metabolized by P450 isoenzymes (e.g., CYP 2C9, CYP 2C19), which is not known to be affected by fruit juices such as grapefruit juice or PJ.

One study examined the effect of PJ on CYP3A-mediated drug metabolism both in vitro and in vivo.126 Among the members of the P450 family, CYP3A is thought to be the most important enzyme and is involved in the majority of P450-catalyzed metabolism. Using liver microsomes, it was found that the addition of PJ inhibited the metabolism of carbamazepine, a drug known to be metabolized by CYP3A. The in vivo interaction between PJ and carbamazepine was then studied in male Wistar rats. Orally consumed PJ was found to increase the AUC when given 1 hour prior to oral administration of carbamazepine. However, when PJ was injected into the bloodstream, there was no effect on the AUC for the drug. The investigators suggest that PJ may impair the function of enteric but not hepatic CYP3A. Similar results on enteric but not hepatic activity were also found in another study with rats examining the effect of PJ on CYP2C9 and tobultamide pharmacokinetics.127

The effect of POM Wonderful PJ and grapefruit juice on CYP3A activity was studied in vitro and in human volunteers.128 Using human liver microsomes and triazolam (a drug metabolized by CYP3A), the investigators found that pre-incubation with grapefruit juice and POM Wonderful PJ led to inhibition of CYP3A. However, a study with healthy human volunteers found that pretreatment with POM Wonderful PJ (8 ounces) did not alter the elimination half-life, volume of distribution, or clearance of intravenous midazolam (another drug metabolized by CYP3A). POM Wonderful PJ also did not affect Cmax, AUC, or clearance of oral midazolam (6 mg). Alternatively, the same amount of oral grapefruit juice was found to impair clearance and elevate plasma levels of oral midazolam. The results of this study suggest that oral consumption of 8 ounces of POM Wonderful PJ does not alter the activity of hepatic or intestinal CYP3A in humans.