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Red wine-cisapride interaction: comparison with grapefruit juice.

E M Offman¹, D J Freeman, G K Dresser

¹Departments of Medicine and Pharmacology and Toxicology, London Health Sciences Centre and the University of Western Ontario, Canada.

Clinical Pharmacology and Therapeutics

|July 14, 2001

Summary

Grapefruit juice significantly increased cisapride levels by inhibiting CYP3A4, while red wine had minimal effects. Individual responses varied, with some showing marked interactions with both substances.

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Area of Science:

Pharmacology
Drug Metabolism
Drug Interactions

Background:

Cisapride is metabolized by cytochrome P450 3A4 (CYP3A4).
Grapefruit juice and red wine are known inhibitors of CYP3A4.

Purpose of the Study:

To compare the pharmacokinetic interactions of grapefruit juice and red wine with cisapride.
To assess the impact on cisapride systemic availability and metabolite formation.

Main Methods:

A randomized, 3-way crossover study in 12 healthy men.
Administration of cisapride (10 mg) with grapefruit juice, red wine, or water.
Measurement of cisapride, norcisapride pharmacokinetics, and QTc interval over 24 hours.

Main Results:

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Grapefruit juice increased cisapride AUC by 151% and C(max) by 168% (P <.01).

Red wine showed minor, non-significant increases in cisapride AUC (115%) and C(max) (107%).

QTc interval remained unchanged; individual variability in response was observed.

Conclusions:

Grapefruit juice significantly increases cisapride bioavailability via CYP3A4 inhibition, with variable individual responses.
Red wine exhibited minimal pharmacokinetic changes, though some CYP3A4 inhibition occurred.
Individuals with high intestinal CYP3A4 activity may experience significant interactions even with moderate red wine consumption.