DRUG ACETYLATION IN LIVER-DISEASE

N-Acetylation is a phase II conjugation reaction mediated in humans by the polymorphic N-acetyltransferase 2 (NAT2) and N-acetyltransferase 1 (NAT1). Acetylation of some drugs may be modestly decreased in patie nts with chronic liver disease, whereas acute liver injury has no effe ct on drug acetylation. For NAT2 substrates, the impairment in acetyla tion capacity seems to be phenotype-specific, with a more prominent ef fect being exerted in rapid than slow acetylators. Thus, in the presen ce of significant hepatic dysfunction, the activity of NAT2 may not ex hibit its usual bimodal distribution, and hence phenotypic assignment may not be reliable. Furthermore, it remains to be evaluated whether t he precautions advised for slow acetylators when treated with drugs me tabolised by NAT2 apply to all patients (regardless of phenotype) with liver cirrhosis.