Clinical Pharmacokinetics

, Volume 34, Issue 3, pp 219–226

Drug Acetylation in Liver Disease

  • Micha Levy
  • Yoseph Caraco
  • Gerd Geisslinger
Review Article Special Populations

Abstract

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.

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Copyright information

© Adis International Limited 1998

Authors and Affiliations

  • Micha Levy
    • 1
  • Yoseph Caraco
    • 1
  • Gerd Geisslinger
    • 2
  1. 1.Clinical Pharmacology Unit, Division of MedicineHadassah University HospitalJerusalemIsrael
  2. 2.Department of Experimental and Clinical Pharmacology and ToxicologyUniversity of Erlangen-NürnbergErlangenGermany

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