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. METHOD: 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). CONCLUSION: 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.
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. METHOD: Forty-six tuberculosispatients 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). CONCLUSION: The results suggest that various NAT2 genotypes in Chinese tuberculosispatients have great impact on the metabolism capacity of NAT2. This finding maybe valuable in the rational use of relevant drugs.
Authors: Feng Li; Pengcheng Wang; Ke Liu; Mariana G Tarrago; Jie Lu; Eduardo N Chini; Xiaochao Ma Journal: Drug Metab Dispos Date: 2016-08-16 Impact factor: 3.922
Authors: A K Hemanth Kumar; K Ramesh; T Kannan; V Sudha; Hemalatha Haribabu; J Lavanya; Soumya Swaminathan; Geetha Ramachandran Journal: Indian J Med Res Date: 2017-01 Impact factor: 2.375
Authors: Paolo Denti; Kidola Jeremiah; Emmanuel Chigutsa; Daniel Faurholt-Jepsen; George PrayGod; Nyagosya Range; Sandra Castel; Lubbe Wiesner; Christian Munch Hagen; Michael Christiansen; John Changalucha; Helen McIlleron; Henrik Friis; Aase Bengaard Andersen Journal: PLoS One Date: 2015-10-26 Impact factor: 3.240