#Grapefruit juice interactions series#

6,7 A recent series of studies have shown that bergamottin is not readily detectable in urine due to extensive metabolism to the metabolites DHB and bergaptol. 5 A number of studies have verified that these compounds are capable of inhibiting CYP3A4 enzymes and may do so in a dose-dependent manner. A number of these compounds exist, but 6’7’ dihydroxybergamottin (DHB), bergamottin, and bergaptol are found at the highest concentrations in grapefruit and grapefruit juice. The group of compounds found in grapefruit that have been identified as contributing to CYP3A4 inhibition are known as furanocoumarins. Subjects reported increased impairment from oxycodone and grapefruit co-ingestion, possibly due to an escalation in serum concentrations of both parent drug and its active metabolite, oxymorphone.įigure 1: Oxycodone cytochrome P450 metabolic pathway Collectively, the results indicated a shift toward the CYP2D6 metabolic pathway caused by reduced CYP3A4 activity. 4 After five days of grapefruit juice and oxycodone ingestion, serum oxycodone and oxymorphone concentrations were increased by 67% and 32%, respectively. 2,3 Elevated serum concentrations could lead to an increased risk of adverse effects such as central nervous system (CNS) depression and cardiotoxicity, especially in those patients that are naive to therapy.Ī similar study detailed the effect of 3A4 inhibition on oxycodone and formation of its metabolites (Figure 1). Statistically significant increases in serum concentrations of methadone were observed. A study of patients receiving maintenance methadone therapy was performed to determine the effect of grapefruit juice on steady state methadone concentrations. Several medications used in pain management are affected by grapefruit-drug interactions. Pharmacokinetic studies have been widely performed to establish this interaction.

As plasma levels increase, so does the opportunity for adverse effects associated with prescribed therapy. Subsequently, inhibition of this pathway can lead to increased plasma levels of parent drug, possibly potentiating the effects of the drug. This metabolic pathway is primarily involved in metabolism of medications to inactive metabolites. CYP3A4 is one of the primary enzymes involved in the metabolism of a multitude of medications. In particular, grapefruit has demonstrated the ability to cause CYP450 3A4 inhibition. Grapefruit products are well-known culprits of drug-food interactions that occur in clinical practice. Grapefruit contains substances known as furanocoumarins, which are capable of inhibiting CYP3A4 enzymes responsible for drug metabolism. Inhibition may result in increased parent drug concentrations or altered metabolite formation, leading to toxicity associated with elevated serum drug levels or therapeutic failure if a patient is taking a prodrug. Q: What is the significance of grapefruit-drug interactions, and how can I most effectively detect if a patient is at risk for negative therapeutic outcomes due to this type of interaction?Ī: Grapefruit is a widely known inhibitor of the CYP450-mediated metabolism of drugs. Grapefruit-Drug Interactions Friday, September 15, 2017

Grapefruit juice interactions