ASSESSMENT OF ARYLAMINE N-ACETYLTRANSFERASE (NAT1) ACTIVITY IN MONONUCLEAR LEUKOCYTES OF CYSTIC-FIBROSIS PATIENTS

The clearance of sulphamethoxazole (SMX), a compound metabolised primarily by the N-acetyltransferase NAT1, is increased in cystic fibrosis (CF) patients. We assessed the activity and kinetic properties of NAT1 in lysates of peripheral blood mononuclear leukocytes (MNL) from CF (n = 17) and control (n = 22) subjects using SMX and p-aminobenzoic acid (PABA) as test substrates, The K-m and V-max values of both substrates in MNL from CF patients and control subjects were not significantly different. The acetylation of PABA (100 mu M) by intact MNL from CF patients (n = 4) was not different from the observed in intact MNL from controls (n = 9) (25 +/- 3 pmol h(-1) per 10(6) MNL vs 27 +/- 4 pmol h(-1) per 10(6) MNL). These results suggest that there are not systemic changes in this enzyme in CE The increased metabolic clearance of SMX may therefore be related to factors other than alterations in the level of activity of the N-acetyltransferase NAT1.