Pharmacokinetics of Amiodarone in hyperlipidemic and simulated high fat-meal rat models.
The objective of this study was to examine the effect of a high fat meal and hyperlipidemia on the pharmacokinetic behavior of amiodarone. To evaluate these effects, single doses of amiodarone were administered to rats i.v. (25 mg/kg) or orally (50 mg/kg). Some rats were rendered hyperlipidemic by intraperitoneal doses of poloxamer 407 followed by amiodarone i.v. In other normolipidemic rats, amiodarone was administered i.v. in a fasted state or after the administration of 1% cholesterol in peanut oil. Amiodarone plasma concentrations were considerably (>11-fold) increased in hyperlipidemia. Substantial decreases were noted in the clearance, volume of distribution and unbound fraction (11.6, 23 and 24.7-fold, respectively) in plasma of hyperlipidemic rats. Oral lipid caused a significant increase in plasma AUC(0-infinity) (1.38-fold) and a significant decrease in clearance (1.5-fold) of amiodarone after intravenous doses. Oral consumption of 1% cholesterol in peanut oil significantly increased the plasma AUC (1.83-fold) and bioavailability of amiodarone (1.31-fold) after oral doses. In determining oral bioavailability of lipophilic drugs such as amiodarone in food effect studies, in addition to the increase in absorption of drugs, other factors such as a decrease in clearance due to increases in lipoprotein levels should be taken into account.
Shayeganpour
Anooshirvan
A
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
Jun
Andrew S
AS
Brocks
Dion R
DR
D000638:Amiodarone / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D001798:Blood Proteins / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage*; D006949:Hyperlipidemias / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D020442:Poloxamer / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001798:Blood Proteins; D004041:Dietary Fats; D008074:Lipoproteins; D020442:Poloxamer; D000638:Amiodarone