抗结核药物利福平不同时间点血药浓度对比分析

Comparative study on serum C_(2h) and C_(4h) of antituberculosis drug rifampicin

目的:分析结核病人在服用抗结核药物利福平后C2h和C4h血药浓度与利福平预期血药浓度(8~24μg·m L^(-1))对比的达标率差异,为临床抗结核药物血药浓度监测提供指导。方法:研究对象分为试验组和对照组,试验组30例结核患者采集服用利福平5~7 d后服药4 h的静脉血,对照组60例C_(2h)血药浓度数据从我院药理研究室数据库收集。其中,血药浓度测定采用高效液相色谱-质谱联用设备,数据分析采用SPSS19.0统计学软件,采用卡方或t检验进行对比分析,P<0.05认为差异具有统计学意义。结果:对两组性别、年龄和血药浓度达标情况做统计学分析。对照组:男28例,女32例,平均年龄(39.6±14.1)岁,C_(2h)为(7.19±2.76)μg·m L^(-1),达标率45%;试验组:男12例,女18例,平均年龄(37.4±11.9)岁,C_(4h)为(10.4±2.79)μg·m L^(-1),达标率76.7%。两组间性别比例及年龄差异无统计学意义(P>0.05),血药浓度及达标率差异均具有统计学意义(P<0.05)。结论:对于利福平,服药4 h后的血药浓度C_(4h)更接近预期血药浓度值。因此,临床需要对患者进行抗结核药物血药浓度监测时采用C4h浓度对临床合理用药更具有指导意义。

Objective： To analyze the difference between blood C2h and C4h and expected blood drug concentration（8 to 24 μg·m L^-1） of rifampicin in TB patients to guide therapeutic drug monitoring in clinic. Methods： The research subjects were divided into experimental group and control group. Blood samples were taken at 4 h from the 30 patients in the experimental group who had taken rifampicin for 5 to 7 d. The C2h levels of 60 patients in the control group were collected from our hospital pharmacology laboratory database. The plasma concentrations of rifampicin were quantified using a validated liquid chromatography tandem mass spectrometry（LC-MS/MS） method developed in our hospital pharmacology laboratory. Chi-square or t-test was conducted on the gender, age and blood drug concentration of the two groups by using SPSS19.0 statistical software, and P〈0.05 was set as significant level. Results： The control group had 28 male and 32 female patients and the experimental group had 12 male and 18 female patients（P〉0.05）. The mean age of the control group was（39.6±14.1） years, and that of the experimental group was（37.4±11.9） years（P〉0.05）. The mean C2h of the control group was（7.19±2.76） μg·m L^-1 and the qualification rate was 45%. The mean C4h of the experimental group was（10.4±2.79） μg·m L^-1 and the qualification rate was 76.7%. There was statistically significant difference（P〈0.05）. Conclusion： The C4h of rifampin is closer to the expected blood concentration than C2h. Therefore, it is more meaningful to refer C4h for clinical rational medication when it is necesssary to monitor the blood drug concentration of rifampicin.