Dose-dependent effect of propafenone on in vivo drug metabolism in the rat.
The effect of propafenone, an investigational antiarrhythmic, on in vivo drug metabolism was examined in the rat using the model substrate antipyrine. Administration of a single oral dose of propafenone 100 mg/kg one hour prior to antipyrine administration resulted in a 23% reduction in antipyrine clearance. Similarly, administration of a dose of 200 mg/kg resulted in a 40% reduction in antipyrine clearance. These data indicate that propafenone, like other agents subject to substantial first-pass metabolism, is capable of inhibiting oxidative drug metabolism in vivo. The dose-dependency of this phenomenon suggests a competitive mechanism.
Chong
M T
MT
Department of Pharmaceutical Sciences, College of Pharmacy & Allied Health Professions, Wayne State University, Detroit, Michigan 48202.
Svensson
C K
CK
D000818:Animals; D000983:Antipyrine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011405:Propafenone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D004364:Pharmaceutical Preparations; D011405:Propafenone; D000983:Antipyrine