Ethanol interaction with drug acetylation in vivo and in vitro

The acute effect of ethanol on sulfadimidine or procainamide pharmacokinetics was studied in healthy drug-free volunteers. Ethanol treatment increased the elimination rate, as well as the amount of acetylated drug measured in blood and urine. No changes of apparent volume of distribution or renal drug clearance were found. In three out of seven slow acetylators tested, the rate of acetylation increased so noticeably after ethanol that they would otherwise have been classified as rapid acetylators. Using suspensions of isolated rat liver parenchymal cells, the effect of ethanol, acetate, citrate, pyruvate, and L(-)carnitine on acetylation of sulfanilamide and procainamide was studied. Ethanol treatment enhanced sulfanilamide acetylation, whereas the acetylation of procainamide was unchanged. Acetate, citrate, and pyruvate treatment enhanced the acetylation of both drugs. Acetate treatment increased both Km and Vmax of both sulfanilamide and procainamide acetylation. In rat liver homogenates, acetyl-CoA increased the rate of sulfanilamide acetylation in a dose-dependent manner.