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Effect of cimetidine on quinidine bioavailability.
J J MacKichan1, H Boudoulas, S F Schaal
1College of Pharmacy, Ohio State University, Columbus 43210.
Biopharmaceutics & Drug Disposition
|January 1, 1989
Summary
Cimetidine increases quinidine levels by reducing its hepatic clearance and also decreasing the amount of quinidine absorbed by the body. This drug interaction study highlights a dual mechanism affecting quinidine bioavailability.
Area of Science:
- Pharmacology
- Drug Metabolism
- Clinical Pharmacy
Background:
- Concurrent administration of cimetidine and quinidine can lead to elevated quinidine serum concentrations.
- Previous studies suggest impaired hepatic clearance due to enzyme inhibition as the primary mechanism.
- The impact on quinidine's bioavailable fraction requires further elucidation.
Purpose of the Study:
- To investigate the effect of cimetidine on the bioavailable fraction of quinidine.
- To elucidate the complete pharmacokinetic interaction between cimetidine and quinidine.
Main Methods:
- Utilized studies in normal volunteers.
- Compared serum concentration-time curves of orally administered quinidine under cimetidine therapy versus control conditions.
Main Results:
- Cimetidine significantly increased the area under the serum concentration-time curve for quinidine.
- Demonstrated that cimetidine decreases the bioavailable fraction of quinidine, in addition to affecting hepatic clearance.
Conclusions:
- Cimetidine exerts a dual effect on quinidine pharmacokinetics: reducing hepatic clearance and decreasing oral bioavailability.
- Clinicians should be aware of this comprehensive interaction when prescribing these drugs concurrently.
- Further research may explore dose adjustments or alternative antiarrhythmic therapies.