Elevation of steady-state diazepam levels by cimetidine

Area of Science:

• Pharmacology
• Drug Metabolism
• Clinical Pharmacology

Background:

• Diazepam is a commonly prescribed anxiolytic and sedative.
• Cimetidine is a histamine H2 receptor antagonist used to treat peptic ulcers.
• Potential drug interactions between cimetidine and other medications are clinically relevant.

Purpose of the Study:

• To investigate the pharmacokinetic effects of cimetidine on steady-state diazepam levels in healthy subjects.
• To determine if cimetidine alters diazepam's total body clearance and elimination half-life.

Main Methods:

• A placebo-controlled study involving six healthy subjects.
• Subjects received a stable daily dose of diazepam (5 mg/day).
• Concomitant administration of cimetidine (1000 mg/day) or placebo for 11 days.

Main Results:

• Cimetidine increased steady-state plasma diazepam concentrations by 40-50% (P < 0.002).
• Total body clearance of diazepam was reduced by cimetidine (P = 0.026).
• Diazepam elimination half-life was significantly prolonged by cimetidine (P = 0.02).

Conclusions:

• Cimetidine significantly inhibits diazepam metabolism.
• The observed interaction leads to increased diazepam exposure and prolonged half-life.
• Caution is advised when co-administering cimetidine and diazepam due to altered pharmacokinetics.