Effect of amiodarone on the disposition of procainamide in the rat

✍ Scribed by Li-Ling Liu; Philip W. Knowlton; Craig K. Svensson

• Publisher: John Wiley and Sons
• Year: 1988
• Tongue: English
• Weight: 533 KB
• Volume: 77
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600770804

✦ Synopsis

We examined the effect of amiodarone on the disposition of procainamide in the rat to determine the mechanism of a reported interaction between amiodarone and procainamide and to determine the effect of amiodarone on drug acetylation. Animals received a 5-d pretreatment with amiodarone hydrochloride (100 mg/kg) or diluent prior to the intravenous administration of 50 mg/kg of procainamide hydrochloride. The plasma clearance, volume of distribution, and half-life of procainamide did not significantly differ between the two groups. The urinary recovery of N-acetylprocainamide was increased by 31% (p less than 0.01) in amiodarone pretreated animals. However, there was no change in the partial clearance of procainamide to N-acetylprocainamide. Neither the renal clearance of procainamide nor N-acetylprocainamide was altered by amiodarone pretreatment. These data suggest that amiodarone interacts with procainamide by reduction of an alternate pathway of elimination, possibly oxidative metabolism.