Interaction between erythromycin and the benzodiazepines diazepam and flunitrazepam

Area of Science:

• Pharmacology
• Drug Interactions
• Clinical Pharmacy

Background:

• Benzodiazepines like diazepam and flunitrazepam are commonly prescribed.
• Erythromycin is a widely used antibiotic.
• Understanding potential drug interactions is crucial for patient safety.

Purpose of the Study:

• To investigate the pharmacokinetic and pharmacodynamic interactions between erythromycin and benzodiazepines (diazepam, flunitrazepam).
• To assess the impact of erythromycin on the absorption, distribution, metabolism, and excretion of diazepam and flunitrazepam.

Main Methods:

• Two randomized, double-blind, cross-over studies were conducted.
• Healthy volunteers received erythromycin for one week.
• Diazepam or flunitrazepam was administered on the fourth day of erythromycin treatment.
• Plasma drug concentrations and psychomotor effects were monitored over 42 hours.

Main Results:

• Erythromycin increased the area under the plasma concentration-time curve (AUC) for both diazepam (15%) and flunitrazepam (25%).
• Erythromycin significantly increased the half-life (t1/2) of flunitrazepam and altered diazepam's plasma concentration over time.
• No significant changes in the psychomotor effects of either benzodiazepine were observed.

Conclusions:

• Erythromycin alters the pharmacokinetics of diazepam and flunitrazepam, likely due to reduced metabolic elimination.
• The observed drug interactions appear to be minor and of limited clinical significance.
• Further research may be warranted to fully elucidate the clinical implications in specific patient populations.