Effects of NAT2 polymorphism on SASP pharmacokinetics in Chinese population.
BACKGROUND
Sulfasalazine (SASP) pharmacologic actions are widely applied in clinical therapy. The role of N-Acetyltransferase 2 (NAT2) in the pharmacokinetics of SASP and its metabolites has not been clarified. We investigated the effects of genetic polymorphism of NAT2 on pharmacokinetic profiles of SASP and its two metabolites, sulfapyridine (SP) and N-acetylsufapyridine (AcSP).


METHODS
Eighteen subjects were recruited and divided into 3 groups by NAT2 genotype: wild type (w/w), heterozygous variant (w/m), homozygous variant (m/m). After taking 1000mg SASP tablets, the plasma concentrations of SASP, SP and AcSP were measured with HPLC method and pharmacokinetic parameters were calculated by using the computing program 3P97.


RESULTS
The AUC(0)(-)(72) and Cmax of SP in m/m subjects were significantly higher than those in w/m and w/w subjects, with the values of 172.57+/-49.42, 103.38+/-39.85, 71.37+/-17.52mg h/l, and 9.65+/-2.34, 6.10+/-1.79, 4.55+/-1.38mg/l, respectively. In contrast, the AUC(0)(-)(72) of AcSP was significantly lower in m/m subjects. The Cmax of AcSP in w/w, w/m and m/m subjects was 12.67+/-3.32, 9.07+/-2.29 and 4.22+/-0.93mg/l, respectively, with significant differences among groups. However, there was no significant difference in any pharmacokinetic parameter of SASP among groups.


CONCLUSIONS
Different NAT2 genotypes, leading to functional heterogeneity of NAT2, may affect pharmacokinetics of SP and AcSP. Therefore, genotyping NAT2 gene before administration would be important in SASP therapy.
Ma
Jing-Jing
JJ
Department of Clinical Pharmacology, Jinling Hospital, Clinical School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, PR China.
Liu
Cun-Gang
CG
Li
Jin-Heng
JH
Cao
Xiao-Mei
XM
Sun
Sheng-Li
SL
Yao
Xuan
X
D000284:Administration, Oral; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D002138:Calibration; D002681:China; D005240:Feasibility Studies; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011786:Quality Control; D013427:Sulfapyridine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D012460:Sulfasalazine / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D055815:Young Adult
C005377:N-acetylsulfapyridine; D012460:Sulfasalazine; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D013427:Sulfapyridine