Abstract

An in vitro study of drug acetylation in whole blood and in leukocyte suspensions from normal human subjects of known acetylator phenotype was done. Both whole blood and leukocytes (incubated for 5 hr at 37°C) acetylate dapsone. No correlation was found between the acetylator phenotype of the subject and the amount of in vitro acetylation of dapsone by whole blood or leukocyte suspensions in plasma as determined by high pressure liquid chromatography. In man, therefore, the N-acetyltransferase present in blood is apparently not of the polymorphic type. Whole blood also deacetylates monoacetyldapsone, but at a slower rate than that for the acetylation of dapsone. This is in agreement with the in vivo situation determined by Gelber et al. (Clin. Pharmacol. Ther. 12, 225 (1971)). Procainamide and p-aminosalicylic acid are also acetylated when incubated in whole blood (6 hr at 37°C). Thin-layer chromatographic analyses of blood extracts from one fast and two slow acetylators indicated no obvious difference in the amount of acetylated metabolite formed from these two drugs. p-Aminosalicylic acid, but not procainamide, was also acetylated by leukocyte suspensions during a 6-hr incubation at 37°C. Hydralazine was nonenzymatically acetylated to 3-methyl-s-triazolo[3,4-a]phthalazine when incubated (18 hr at 37°C) in human plasma ultrafiltrate or Ringer’s solution buffered to pH 7.4. both containing an equimolar amount of acetyl-CoA. This metabolite and the acetylated metabolites from the whole blood incubation of dapsone and procainamide were identified in part from mass spectral data.