Effect of amiodarone on the pharmacokinetics of phenytoin, quinidine, and lidocaine in the rat.
Previous studies have shown that amiodarone can depress certain aspects of hepatic drug metabolism in the rat. This effect was assessed in vivo by investigating the single dose intravenous pharmacokinetics of phenytoin (10 mg/kg), quinidine (25 mg/kg) and lidocaine (7.5 mg/kg) in rats pretreated for three days with a single daily 100 mg/kg intraperitoneal dose of amiodarone hydrochloride. Compared to vehicle treated controls, significant reductions of 61% and 35% in the respective total clearances of phenytoin and quinidine were observed in the presence of amiodarone. Likewise, the elimination half-lives of phenytoin and quinidine were also significantly prolonged after amiodarone pretreatment. Lidocaine pharmacokinetic parameters were unchanged in the presence of amiodarone. These results suggest that altered hepatic drug clearance may play a part in the recently described clinical drug interactions between amiodarone and either phenytoin or quinidine.
D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D006207:Half-Life; D007700:Kinetics; D008012:Lidocaine / Q000097:blood*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010672:Phenytoin / Q000097:blood*; D011802:Quinidine / Q000097:blood*; D051381:Rats; D011919:Rats, Inbred Strains
D001572:Benzofurans; D010672:Phenytoin; D008012:Lidocaine; D011802:Quinidine; D000638:Amiodarone