Arylamine N-acetyltransferases and drug response

Arylamine N-acetyltransferases (NATs) play an important role in the interaction of competing metabolic pathways determining the fate of and response to xenobiotics as therapeutic drugs, occupational chemicals and carcinogenic substances. Individual susceptibility for drug response and possible adverse drug reactions are modulated by the genetic predisposition (manifested for example, by polymorphisms) and the phenotype of these enzymes. For all drugs metabolized by NATs, the impact of different in vivo enzyme activities is reviewed with regard to therapeutic use, prevention of side effects and possible indications for risk assessment by phenotyping and/or genotyping. As genes of NATs are susceptibility genes for multifactorial adverse effects and xenobiotic-related diseases, risk prediction can only be made possible by taking the complexity of events into consideration.