Grapefruit juice interaction with oral budesonide: equal effect on immediate-release and delayed-release formulations

Area of Science:

• Pharmacology
• Drug Metabolism
• Gastroenterology

Background:

• Grapefruit juice (GFJ) is known to inhibit CYP3A enzymes in the gut wall.
• This inhibition reduces the first-pass metabolism of drugs metabolized by CYP3A.
• Budesonide is a drug primarily metabolized by CYP3A.

Purpose of the Study:

• To investigate the effect of GFJ on the systemic availability of budesonide.
• To compare the influence of GFJ on both extended-release (ER) and plain budesonide capsules.
• To assess if GFJ alters budesonide's bioavailability through gut wall or hepatic inhibition.

Main Methods:

• An open crossover study involving eight healthy male participants.
• Participants received 3 mg of budesonide (ER or plain capsules) with or without prior GFJ intake.
• GFJ (200 ml) was administered thrice daily for four days.
• A simultaneous intravenous low dose of deuterium-labeled budesonide was used to estimate bioavailability and rule out hepatic inhibition.
• Plasma concentrations of labeled and unlabeled budesonide were measured.

Main Results:

• GFJ intake did not affect the systemic clearance of budesonide.
• Bioavailability of budesonide was approximately doubled following GFJ consumption.
• This effect was observed for both the extended-release and plain capsule formulations.
• Absorption of the ER formulation occurs in the lower gastrointestinal tract where CYP3A activity is lower.

Conclusions:

• Regular consumption of grapefruit juice doubles the bioavailability of both plain and delayed-release budesonide.
• This interaction is likely due to the inhibition of CYP3A activity in the intestinal mucosa by grapefruit juice.
• Clinicians should consider this interaction when prescribing budesonide to patients consuming grapefruit juice.