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Propranolol interactions with diazepam, lorazepam, and alprazolam
Clinical Pharmacology and Therapeutics
|October 1, 1984
Summary
Propranolol reduces diazepam clearance but does not affect lorazepam or alprazolam metabolism. This beta-blocker impacts how the body processes certain benzodiazepines, highlighting drug interaction risks.
Area of Science:
- Pharmacology
- Clinical Pharmacology
- Drug Metabolism
Background:
- Benzodiazepines like diazepam, lorazepam, and alprazolam are commonly prescribed.
- Propranolol is a beta-blocker frequently used for cardiovascular conditions.
- Potential drug interactions between benzodiazepines and propranolol warrant investigation.
Purpose of the Study:
- To investigate the pharmacokinetic interaction between propranolol and three benzodiazepines: diazepam, lorazepam, and alprazolam.
- To determine if propranolol affects the elimination half-life and clearance of these benzodiazepines.
Main Methods:
- Healthy subjects received diazepam, lorazepam, or alprazolam with and without propranolol.
- Propranolol regimen compliance was verified by serum levels and reduced metaproterenol sensitivity.
- Pharmacokinetic parameters including elimination half-life (t1/2) and clearance were measured.
Main Results:
- Propranolol significantly prolonged diazepam's elimination t1/2 and reduced its clearance.
- Propranolol increased the area under the curve (AUC) for desmethyldiazepam, a major diazepam metabolite.
- Propranolol did not significantly alter the t1/2 or clearance of lorazepam or alprazolam.
Conclusions:
- Propranolol impairs diazepam clearance, likely due to inhibition of N-demethylation.
- Propranolol does not affect lorazepam clearance via glucuronide conjugation.
- Propranolol does not affect alprazolam clearance via aliphatic hydroxylation, suggesting specific metabolic pathways are involved.