title: Estimating N-acetyltransferase metabolic activity and pharmacokinetic parameters of isoniazid from genotypes in Chinese subjects.
abstract: BACKGROUND
  To establish quantitative relationship between metabolic activity of N-acetyltransferase (NAT2) and single nucleotide polymorphisms (SNPs), and estimate pharmacokinetic parameters of isoniazid (INH) on the basis of NAT2 alleles in Chinese subjects.
  
  
  METHODS
  Concentrations of INH and acetylisoniazid in plasma of 24 subjects were measured 0-14 h after oral administration of INH. Pharmacokinetic parameters were simulated. NAT2 alleles were determined by a reversed dot blot method. Correlation between various NAT2 SNPs and metabolic ratio (MR) or INH pharmacokinetic parameters was studied by multiple linear regression analysis.
  
  
  RESULTS
  There was quantitative relationship between various NAT2 alleles and MR of sulphadimidine (r(2)=0.836, P<0.0001). The pharmacokinetic parameters such as k, C(max), AUC, Cl of INH and C(max), AUC of AcINH can be calculated by NAT2 variant patterns. There was good correlation between observed and calculated data (r(2)>0.75, P<0.0001) except for C(max) of INH (r(2)=0.35, P=0.021). The 95% confidence intervals for prediction error ranged from -3.3%-5.6% for k to -10.5%-37.0% for C(max) of INH.
  
  
  CONCLUSIONS
  NAT2 genotypes can be used to predict pharmacokinetic parameters of INH. It may be useful in the rational use of INH.
authors.affiliation: Department of Clinical Pharmacology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200025, PR China. chchenbing@hotmail.com
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.forename: Weimin
authors.initials: W
authors.lastname: Cai
authors.forename: Jinheng
authors.initials: J
authors.lastname: Li
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Cao