Food-drug interactions: grapefruit juice

Area of Science:

• Pharmacology
• Drug Metabolism
• Clinical Pharmacy

Background:

• Food-drug interactions (FDIs) are clinically significant, affecting oral drug bioavailability.
• Grapefruit juice (GFJ) is a common dietary substance known to cause numerous FDIs.
• These interactions can lead to reduced therapeutic effects or increased adverse drug reactions.

Purpose of the Study:

• To elucidate the mechanisms by which GFJ influences drug pharmacokinetics.
• To identify the specific compounds in GFJ responsible for these interactions.
• To highlight the clinical implications of GFJ consumption with medications.

Main Methods:

• Review of existing literature on GFJ and drug interactions.
• Analysis of the biochemical pathways involved in GFJ-mediated drug metabolism inhibition.
• Identification of key chemical constituents in GFJ responsible for pharmacokinetic alterations.

Main Results:

• GFJ inhibits pre-systemic drug metabolism via gut wall CYP3A4 isoenzymes.
• GFJ affects drug bioavailability by inhibiting efflux transporters like P-glycoprotein (P-gp), MRP2, and OATP.
• Furanocoumarins, such as 6',7'-dihydroxybergamottin and bergamottin, are the primary active compounds in GFJ responsible for these interactions.
• Flavonoids like naringin and naringenin are present but furanocoumarins are crucial for maximal inhibitory effects.

Conclusions:

• Furanocoumarins in GFJ are essential for its drug interaction potential, acting through inhibition of metabolic and transport proteins.
• GFJ consumption can significantly alter the efficacy and safety profile of various orally administered drugs.
• Other citrus fruits and furanocoumarin-containing plants may also pose similar risks for drug interactions.