N-乙酰化酶2基因型对中国肺结核患者异烟肼代谢的影响  

Impact of N-acetyltransferase 2 genotypes on the metabolism of isoniazid in Chinese pulmonary tuberculosis patients

作　　者：陈冰[1] 许亦鸣[2] 曹晓梅[3] 李金恒[3] 

机构地区：[1]上海交通大学医学院附属瑞金医院药剂科,上海200025 [2]南京胸科医院药剂科,南京210000 [3]南京军区南京总医院临床药理科,南京210002

出　　处：《中国临床药学杂志》2008年第1期35-38,共4页Chinese Journal of Clinical Pharmacy

基　　金：国家自然科学基金(批准号:30472055);江苏省卫生厅科技发展基金(200309)资助

摘　　要：目的研究N-乙酰化酶2(NAT2)基因型对中国肺结核患者异烟肼(INH)代谢的影响。方法采用反向点交法(RDB)检测中国肺结核患者NAT2基因型;柱前衍生化高效液相色谱法检测服药2 h后血浆中INH及其代谢物乙酰化INH(Ac- INH)浓度。结果46例患者基因型包括野生型wt/wt(n=17)、杂合子m/wt(n=22)、突变型纯合子m/m(n=7)。血浆INH及AcINH浓度分别为(12.74±10.51)和(12.49±9.61)μmol·L^(-1)。3个基因组INH、AcINH浓度比为1:1.37:1.77和1:0.77:0.75;3组AcINH与INH比值(R_(A/I))为1:0.52:0.40(P<0.01)。结论不同NAT2基因型的结核患者对INH代谢能力差异显著,存在基因剂量现象。NAT2基因分型对结核患者合理用药具有重要意义。A/M To study the influence of N-acetyltransferase 2 （NAT2） genotypes on the metabolism of isoniazid （INH） in Chinese pulmonary tuberculosis patients. METHODS NAT2 genotypes of tuberculosis patients were detected by a reverse dot blot （RDB） method. The plasma concentration of INH and its major metabolite acetyl-isoniazid （AcINH） was determined by a precolumn deriviation HPLC method 2 h after administration of INH. RESULTS Fortysix tuberculosis patients were classified as 17 homozygous wild types （wt/wt）, 22 heterozygous mutants （m/wt） and 7 homozygous mutants （m/m）. The plasma concentration of INH and AcINH was （ 12.74 ± 10.51） and （12.49 ± 9.61） μmol· L^- 1, respectively. Concentration of INH and AcINH in wt/wt, m/wt and m/m groups were 1 ： 1.37 ： 1.77 and 1 ： 0.77：0.75,respectively. The ratio of AcINH and INH （RA/I） in 3 groups was 1：0.52：0.40 （P 〈 0.01）. CONCLUSION There is significant difference of metabohsm of INH in tuberculosis patients with different NAT2 genotypes. It seems that there is gene dose effects. Genotyping of NAT2 may be valuable in the rational use of relevant drugs in tuberculosis patients.

关 键 词：异烟肼 乙酰异烟肼 N-乙酰化酶2 基因剂量 肺结核 

分 类 号：R521[医药卫生—内科学]