Drug Acetylation in Liver Disease
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- Levy, M., Caraco, Y. & Geisslinger, G. Clin Pharmacokinet (1998) 34: 219. doi:10.2165/00003088-199834030-00004
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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 patients with chronic liver disease, whereas acute liver injury has no effect on drug acetylation. For NAT2 substrates, the impairment in acetylation capacity seems to be phenotype-specific, with a more prominent effect being exerted in rapid than slow acetylators. Thus, in the presence of significant hepatic dysfunction, the activity of NAT2 may not exhibit its usual bimodal distribution, and hence phenotypic assignment may not be reliable. Furthermore, it remains to be evaluated whether the precautions advised for slow acetylators when treated with drugs metabolised by NAT2 apply to all patients (regardless of phenotype) with liver cirrhosis.