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Interaction between grapefruit juice and midazolam in humans
H H Kupferschmidt1, H R Ha, W H Ziegler
1Division of Clinical Pharmacology and Toxicology, University Hospital, Zürich, Switzerland.
Clinical Pharmacology and Therapeutics
|July 1, 1995
Summary
Grapefruit juice significantly increases oral midazolam bioavailability and alters its pharmacodynamics, potentially impacting clinical use, especially in vulnerable patients. This interaction warrants careful consideration.
Area of Science:
- Pharmacology
- Drug Interactions
- Clinical Pharmacokinetics
Background:
- Midazolam is a widely used sedative and anesthetic agent.
- Grapefruit juice is known to inhibit cytochrome P450 enzymes, potentially affecting drug metabolism.
- Understanding drug interactions is crucial for safe and effective patient care.
Purpose of the Study:
- To evaluate the impact of grapefruit juice on the pharmacokinetics and pharmacodynamics of midazolam.
- To determine if grapefruit juice alters midazolam absorption, metabolism, or effects.
Main Methods:
- An open-label, crossover study involving eight healthy male subjects.
- Subjects received either intravenous or oral midazolam after pretreatment with water or grapefruit juice.
- Pharmacokinetic parameters (Cmax, tmax, AUC) and pharmacodynamic measures (reaction time, DSST) were assessed.
Main Results:
- Grapefruit juice did not affect intravenous midazolam pharmacokinetics or pharmacodynamics.
- Oral midazolam showed increased Cmax (56%), tmax (79%), and AUC (52%) after grapefruit juice pretreatment.
- Bioavailability of oral midazolam increased from 24% to 35% with grapefruit juice; alpha-hydroxymidazolam AUC also increased.
Conclusions:
- Grapefruit juice significantly increases oral midazolam bioavailability.
- Pharmacodynamic effects of oral midazolam are altered by grapefruit juice, with prolonged onset.
- These findings suggest potential clinical significance, especially in patients with factors increasing midazolam bioavailability.