Inter-individual variation of human blood N-acetyltransferase activity in vitro.
Inter-individual variation in the in vitro acetylation of the antibacterial drug sulphamethazine by human whole blood was studied using reverse phase HPLC. The mean (range) values of blood N-acetyltransferase activity in vitro were 0.50 (0.29-0.83) nmol per 10(9) red blood cells (rbc) (N = 23), 3.33 (2.22-5.27) nmol per 10(9) rbc (N = 27) and 9.36 (6.72-15.76) nmol per 10(9) rbc (N = 23) at initial sulphamethazine concentrations of 0.018 mM, 0.18 mM and 1.44 mM respectively. The mean (range) values of the initial rate of sulphamethazine acetylation at these substrate concentrations were 28.1 (20.9-35.0) pmol/hr per 10(9) rbc (N = 11), 0.26 (0.18-0.42) nmol/hr per 10(9) rbc (N = 19) and 0.91 (0.61-1.50) nmol/hr per 10(9) rbc (N = 14) respectively. The mean (range) half life of thermal inactivation of blood acetylation capacity at 50 degrees was 0.91 (0.59-1.27) min (N = 12) at an initial substrate concentration of 0.18 mM. In each of these cases, there was no significant differences between the values obtained using blood samples from rapid and slow acetylators. Intra-individual variation of blood N-acetyltransferase activity was studied in a single subject on 24 separate occasions during a two year period and was less than 10% at each of the three sulphamethazine concentrations studied. The correlation between the in vitro blood N-acetyltransferase activity of eight volunteers measured on two separate occasions at least 6 weeks apart was 0.84, 0.98 and 0.98 at initial sulphamethazine concentrations of 0.018 mM, 0.18 mM and 1.44 mM respectively. Increasing the acetyl-CoA concentration of blood samples from 4 subjects by 0.34, 0.85 and 1.67 mM significantly increased both the initial acetylation rate of sulphamethazine and the amount of acetylsulphamethazine produced after an incubation time of 24 hr (initial sulphamethazine concentration = 0.18 mM).
Lindsay
R M
RM
Department of Biochemical Medicine (University of Dundee), Ninewells Hospital and Medical School, Scotland, U.K.
Baty
J D
JD
D000105:Acetyl Coenzyme A / Q000494:pharmacology; D000107:Acetylation; D000123:Acetyltransferases / Q000097:blood*; D000328:Adult; D001191:Arylamine N-Acetyltransferase / Q000097:blood*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged
D000105:Acetyl Coenzyme A; D000123:Acetyltransferases; D001191:Arylamine N-Acetyltransferase