The influence of NAT2 genotypes on the plasma concentration of isoniazid and acetylisoniazid in Chinese pulmonary tuberculosis patients.
BACKGROUND
Isoniazid (INH) is widely used in the therapy of tuberculosis. Poor metabolizer (PM) of the NAT2 is an important reason of inter-individual difference of the plasma INH concentration. We studied the relationship between NAT2 genotype and INH and its metabolite acetylisoniazid (AcINH) concentration in Chinese people.


METHODS
Forty-six tuberculosis patients were enrolled in the study. Each patient took 300 mg INH daily for at least 7 days. Two hours after the INH was given, the vein blood was drawn. NAT2 genotypes of patients were detected by a reverse dot blot (RDB) method. The plasma concentration of INH and AcINH was determined by a precolumn derivation HPLC method.


RESULTS
In 46 patients, homozygous mutant (m/m), heterozygous mutant (m/wt) and homozygous wild-type (wt/wt) subjects were 7, 22 and 17, respectively. Plasma concentration of INH and AcINH were 12.74+/-10.51 and 12.49+/-9.61 micromol/l, respectively. There was no statistical difference among 3 genotypes. The ratios of AcINH and INH (R(A/I)) of 3 genotypes were 0.67+/-0.34, 0.88+/-0.40 and 1.69+/-0.66, respectively. The R(A/I) of m/m and m/wt group were significantly lower than wt/wt group (P<0.01).


CONCLUSIONS
The results suggest that various NAT2 genotypes in Chinese tuberculosis patients have great impact on the metabolism capacity of NAT2. This finding maybe valuable in the rational use of relevant drugs.
Chen
Bing
B
Department of Clinical Pharmacology, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, PR China.
Li
Jin-Heng
JH
Xu
Yi-Min
YM
Wang
Jie
J
Cao
Xiao-Mei
XM
D000995:Antitubercular Agents / Q000097:blood* / Q000627:therapeutic use; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D002681:China; D002851:Chromatography, High Pressure Liquid; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007538:Isoniazid / Q000031:analogs & derivatives* / Q000097:blood* / Q000627:therapeutic use; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000235:genetics*
D000995:Antitubercular Agents; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; C510884:acetylisoniazid; D007538:Isoniazid