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The racemic metoprolol H2-antagonist interaction
S Toon1, E M Davidson, F M Garstang
1Pharmacokinetic Department, Medeval Ltd., University of Manchester, UK.
Clinical Pharmacology and Therapeutics
|March 1, 1988
Summary
Cimetidine increased metoprolol bioavailability by inhibiting first-pass metabolism, particularly affecting the less active R-enantiomer. Ranitidine showed no significant impact on metoprolol
Area of Science:
- Pharmacology
- Drug Interactions
- Clinical Pharmacology
Background:
- Metoprolol is a widely used beta-blocker.
- Cimetidine and ranitidine are H2-receptor antagonists that can affect drug metabolism.
- Understanding drug interactions is crucial for patient safety and effective treatment.
Purpose of the Study:
- To investigate the effects of cimetidine and ranitidine on metoprolol pharmacokinetics and pharmacodynamics.
- To assess the impact on both racemic metoprolol and its individual enantiomers.
- To determine the clinical significance of these potential interactions.
Main Methods:
- A pharmacokinetic and pharmacodynamic study was conducted in 12 healthy male volunteers.
- Multiple doses of metoprolol were administered concomitantly with cimetidine or ranitidine.
- A stereoselective assay was used to analyze metoprolol enantiomers.
Main Results:
- Ranitidine did not alter the pharmacokinetics or pharmacodynamics of metoprolol.
- Cimetidine significantly increased metoprolol bioavailability by inhibiting first-pass metabolism.
- This effect was stereoselective, primarily impacting the less pharmacologically active (R)-metoprolol enantiomer.
Conclusions:
- Cimetidine, but not ranitidine, interacts with metoprolol, increasing its bioavailability.
- The interaction is mediated by inhibition of hepatic enzymes involved in metoprolol's first-pass elimination.
- Clinicians should consider this interaction when prescribing metoprolol with cimetidine, especially due to its stereoselective nature.