Interaction between Drug Acetylation and Ethanol, Acetate, Pyruvate, Citrate, and L(minus;)Carnitine in Isolated Rat Liver Parenchymal Cells

Abstract

Absrracf:The actylation of sulfanilamide and procainamide in suspensions of isolated rat parenchymal cells was studied in absence and presence of ethanol (33 mM), acetate (0.5-5 mM), citrate (4 mM), pyruvate (4 mM), and L(-)carnitine (2 mM). Ethanol treatment enhanced the sulfanilamide acetylation whereas the acetylation of procainamide was considered to be unchanged. Acetate(1-5 mM), citrate, andpyruvate treatment enhanced the acetylation of both sulfanilamide and procainamide. Acetate (4 mM) increased both K, and Vmax of both sulfanilamide and procainamide acetylation. Combined treatment with L(-)carnithe and either acetate, pyruvate, or citrate enhanced the acetylation rate of sulfanilamide more than acetate, pyruvate, or citrate, respectively alone. In cell suspensions treated with L(-)carnitine and acetate or pyruvate, the acetylation kinetics of sulfanilamide changed from zero-to apparent first-order. With procainamide as test drug, a further increase of the acetylation rate was found when L(-)carnithe was added to citrate or pyruvate. Acetyl-CoA increased the rate of sulfanilamide acetylation in rat liver homogenates in a dose dependent manner.

Lack of Drug Acetylation in Human Blood Monocytes and Macrophages in Vitro

“…used in this experiment to produce sufficient amount of acetyl-CoA, which is necessary for drug acetylation(Olsen 1982b) could explain our present results. However, a lack of the enzyme, NAT.…”