不同剂型利福平投药后血药浓度的监测结果分析

目的 分析两种不同剂型利福平投药后血药浓度的监测结果,以指导临床合理用药。方法 选择2016年5月至2017年6月昆明市第三人民医院结核二科收治的活动性肺结核患者130例,按照数字表法随机分为注射组(65例;利褔平采用静脉滴注的方式,0.6g/次,1次/d,用500ml 5%葡萄糖注射液配制)和口服组(65例;利褔平采用口服的方式,0.6g/次,1次/d);利福平最低抑菌浓度(MIC)为0.39~1.56μg/ml,本研究统计达到MIC为0.39μg/ml的患者例数。口服组最终有2例患者因不同时间点血药浓度监测数据存在遗漏,故剔除,本研究最终纳入128例患者,其中注射组65例,口服组63例。两组患者用药第7天后,采集不同时间点的血浆标本,通过超高效液相色谱-串联质谱法(UPLC-MS/MS)检测两组利福平的血药浓度值。结果 注射组利福平最高血药浓度出现在输注后1.5h,中位数(四分位数)M(Q₁,Q₃)]为0.954(0.210,3.420)μg/ml;口服组最高血药浓度出现在服药后2h,M(Q₁,Q₃)为1.253(0.249,2.501)μg/ml。注射组峰值血药浓度为1.786(0.704,3.591)μg/ml,均值血药浓度为0.688(0.269,1.087)μg/ml,均高于口服组分别为1.468(0.423,3.748)μg/ml和0.571(0.149,1.894)μg/ml],但差异均无统计学意义(Z值分别为-0.90和-0.02,P值分别为0.366和0.980);注射组谷值血药浓度为0.004(0.001,0.038)μg/ml,低于口服组0.007(0.001,0.070)μg/ml],差异有统计学意义(Z=-8.74,P=0.000)。注射组总体达到MIC的比率为47.7%(248/520),口服组为49.4%(218/441),差异无统计学意义(χ²=0.29,P=0.591)。结论 患者采用注射和口服利福平的治疗方案,血药浓度值均较低,有超过50%的患者总体时间内并未达到MIC,无法满足利福平推荐的参考范围,可能存在剂量上的不足;应继续加强对利福平血药浓度的监测,规范使用利福平注射液。

Analysis on the monitoring results of plasma-drug concentration of rifampicin in different dosage forms

Objective To analyze the monitoring results of plasma-drug concentration of rifampicin in two different dosage forms and provide guidance for clinical proper drug use.Methods A hundred and thirty patients with active pulmonary tuberculosis (PTB), who received treatment in the Second Department of Tuberculosis of the Third People’s Hospital of Kunming from May 2016 to June 2017 were selected. Based on the principle of random number table, the enrolled patients were divided into an injection group (65 cases, rifampicin was given by intravenous drip, 0.6 g per time, once a day, with 500 ml 5% glucose injection) and an oral group (65 cases, rifampicin was administered orally, 0.6 g per time, once a day). The minimum inhibitory concentration (MIC) of rifampicin was 0.39-1.56μg/ml and the patients who reached the MIC of 0.39μg/ml were counted in this study. In the oral group, 2 patients were excluded because of the omission of the blood concentration monitoring data at different time points. So the study eventually included 128 patients, including 65 cases in the injection group and 63 cases in the oral group. After seven days of medication, plasma samples of the patients in two groups were collected in different time periods and the plasma-drug concentration of rifampicin in the two groups was tested by using UPLC-MS/MS.Results For the injection group, the highest concentration of rifampicin occurred at one hour and a half after injection, with a Median (Quartiles) (M (Q₁, Q₃)) of 0.954 (0.210, 3.420)μg/ml; for the oral group, it occurred at two hours after taking the medicine, with a Median (Quartiles) (M (Q₁, Q₃)) of 1.253 (0.249, 2.501)μg/ml. The peak and mean plasma-drug concentrations of rifampicin in the injection group were 1.786 (0.704, 3.591)μg/ml and 0.688 (0.269, 1.087)μg/ml, which were higher than those in the oral group (1.468 (0.423, 3.748)μg/ml and 0.571 (0.149, 1.894)μg/ml), but there was no statistical difference between the two groups (Z=-0.90 and -0.02; P=0.366 and 0.980). The valley plasma-drug concentration in the injection group (0.004 (0.001, 0.038)μg/ml) was lower than that in the oral group (0.007 (0.001, 0.070)μg/ml), and the difference between the two groups was a statistically significant (Z=-8.74, P=0.000). The total rate that the plasma-drug concentration reached MIC in the injection group was 47.7% (248/520) while that was 49.4% (218/441) in the oral group, there was no statistical difference between the two groups (χ ²=0.29, P=0.591).Conclusion The rifampicin treatment is given to the PTB patients either by injection or oral, the plasma-drug concentration of rifampicin all remains low. It fails to reach MIC in more than half of the patients and the internationally recommended reference range cannot be met. It may be coursed by inadequate dose. So he monitoring to the plasma-drug concentration of rifampicin should be strengthened and the use of rifampicin injection should be regulated.