| The purpose of the research is to study the correlation betweenN-acetyltransferase2(NAT2) genotype and the concentrations of isoniazid(INH), p-aminosalicylic acid (PAS-INH), rifampicin (RFP) andPyrazinamide (PZA) in the plasma at2h after tuberculosis (TB) patientstaking first-line antituberculosis drugs and the liver function abnormalitycaused by antituberculosis drugs, so as to provide a basis for the guidanceof rational use of first line antituberculosis drug by NAT2genotyping.The concentration of INH, PAS-INH, RFP and PZA in the plasmafrom77TB cases was determined by a high-performance liquidchromatography (HPLC) at2h after TB patients taking antituberculosisdrugs. The genomic DNAs of blood cells were extracted, and then NAT2genotypes were analyzed by PCR-direct sequencing (PCR-DS). And theresults of liver function tests in patients were recorded before and aftertaking the anti-TB drugs, then the liver function was determined accordingto the liver damage standard.Among77cases of hospitalized tuberculosis patients after takinganti-TB drugs,3patients (3.9%) suffered patients with liver injury,23(29.9%) had abnormal liver function,51(66.2%) had normal liverfunction. Among the77TB patients,47took isoniazid tablets, and theiraverage concentration of INH in the plasma was (3.33±1.79) mg· L-1;19took isoniazid aminosalicylate tablets,and their average concentration ofINH in the plasma was (1.29±1.25) mg· L-1;34took Rifampicin capsules,and their average concentration of RFP in the plasmas was (6.60±2.22) mg· L-1;45took pyrazinamide tablets, and their average concentration ofPZA in the plasma was (15.45±5.61) mg· L-1.Of the77TB cases,25(33.0%) were rapid acetylation (RA) genotype,and their average concentration of INH in the plasma was (2.71±1.35)mg·L-1(14took isoniazid tablets); that of INH was (0.54±0.18) mg·L-1(7took isoniazid aminosalicylate tablets); that of RFP was (6.33±2.47)mg·L-1(11took Rifampicin capsules); that of PZA was (15.82±5.97) mg·L-1(12took pyrazinamide tablets).40cases (51.6%) were intermediateacetylation (IA) genotype, and their average concentration of INH in theplasma was (3.10±1.56) mg·L-1(25took isoniazid tablets); that of INH was(1.25±0.98) mg·L-1(9took isoniazid aminosalicylate tablets); that of RFPwas (6.44±2.03) mg·L-1(18took Rifampicin capsules); that of PZA was(15.47±6.01) mg·L-1(27took pyrazinamide tablets).12cases (15.6%) wereslow acetylation (SA) genotype, their average concentration of INH in theplasma was (5.13±2.14) mg·L-1(8took isoniazid tablets); that of INH was(3.15±1.71) mg·L-1(3took isoniazid aminosalicylate tablets);that of RFPwas (7.78±2.40) mg·L-1(5took Rifampicin capsules); that of PZA was(14.63±3.21) mg·L-1(6took pyrazinamide tablets).The INH plasma concentration in the patients after taking INH withSA-type had significant differences with those with RA-type (P=0.017, P＜0.05), all the other differences had no significant differences (P>0.05).The INH plasma concentration in the patients after taking PAS-INH withSA-type had significant differences with those with RA-and IA-type(P=0.009,0.019, respectively, P＜0.05), but IA-type with RA-type had nosignificant differences (P＞0.05). The PZA and RFP plasma concentrationin the patients with RA-type had no significant differences with those withIA-and SA-type (RA vs IA, RA vs SA and IA vs SA, P>0.05).Among77TB patients there are25with NAT2RA-type. And amang31cases,21(84.0%) were liver function normal,4(16.0%) liver functionabnormal, and no patients had ATDILI. There were40with NAT2IA-type. And among40cases,26(65.0%) were liver function normal,12(30.0%)liver function abnormal,2had ATDILI. There were12with NAT2SA-type. Amang them,4(33.3%) were liver function normal,7(58.3%)liver function abnormal,1(8.3%) had ATDILI; RA-type have asignificantly higher incidence of liver function abnormalities than SA-typecases (P=0.008, P<0.05).The INH, PAS-INH, RFP and PZA plasma concentration wasunrelated to ATDILI. NAT2gene SA-type may result in higher plasmaconcentrations of INH. RA-type has higher incidence of abnormal liverfunction than SA-type. NAT2genotyping may have important guidingsignificance for rational use of first line antituberculosis drug in the TBpatients. |
PDF Full Text Request