Effect of amiodarone on the disposition of procainamide in the rat.
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.
Liu
L L
LL
Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, Wayne State University, Detroit, MI 48202.
Knowlton
P W
PW
Svensson
C K
CK
D000284:Administration, Oral; D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D004347:Drug Interactions; D006207:Half-Life; D008297:Male; D011342:Procainamide / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains
D011342:Procainamide; D000638:Amiodarone