盐酸去甲万古霉素的脑脊液药动学与临床疗效的相关性分析  

Correlation analysis of pharmacokinetics of norvancomycin in cerebrospinal fluid and clinical efficacy

作　　者：邓四军[1] 万永占[2] 

机构地区：[1]北京市大兴区人民医院药剂科,102600 [2]河北医科大学第二医院药剂科

出　　处：《中国医药》2015年第10期1542-1544,共3页China Medicine

基　　金：河北省卫生厅课题（20130465）

摘　　要：目的 探讨盐酸去甲万古霉素的脑脊液药动学与临床疗效的相关性.方法 选择2014年2-12月北京市大兴区人民医院耐甲氧西林金黄色葡萄球菌感染青年患者40例作为研究对象,所有患者接受单剂注射用盐酸去甲万古霉素0.8g静脉滴注,测定与计算脑脊液中去甲万古霉素的药物浓度与药动学情况,并与临床疗效进行相关性分析.结果 去甲万古霉素的脑脊液溶液高浓度标准曲线范围（64±4） mg/L,线性回归方程Y=8.371 3X±6.845 7,r=0.999 1,日内相对标准偏差≤4.58％,日间相对标准偏差≤5.38％,周间相对标准偏差≤7.93％.患者静脉滴注去甲万古霉素0.8g结束后即刻脑脊液药物浓度为（43.6 ±7.0） mg/L,1h内降至峰浓度的50％以下,为（22.9 ±4.2）mg/L,12h和24 h后的平均血药浓度分别为（6.5±1.3） mg/L和（3.1±0.9） mg/L,36 h全部患者的脑脊液药物浓度均高于最低检测浓度（1.0 mg/L）,平均（1.8±0.4） mg/L.药物的半衰期、表观分布容积、药时曲线下面积、药物总清除率与24 h肾清除率分别为（0.35±0.08）h、（9.9±2.2）L、（198 ±20） mg/L＆#183;h、（87±22） ml/min、（76±17） ml/min.治疗后40例患者总有效率为90.0％ （36/40）,治疗过程中无不良反应发生.线性回归方程分析显示去甲万古霉素的药时曲线下面积与药物总清除率为影响临床疗效的主要危险因素（比值比=1.893、2.154,P＜0.05）.结论 盐酸去甲万古霉素的药动学参数与临床疗效有明显相关性,在临床使用中应进行脑脊液药物浓度与药动学监测,据此调整给药方案,从而改善患者预后.Objective To analyze the correlation between pharmacokinetics of norvancomycin in cerebrospinal fluid （CSF） and clinical efficacy.Methods Totally 40 young patients suffering from methicillin resistant staphylococcus aureus infection from February to December 2014 were given a single dose of vancomycin intravenous infusion （0.8 g）.The norvancomycin drug concentration in CSF was measured;the pharmacokinetic data were calculated and their correlations with the efficacy were analyzed.Results The high vancomycin concentration range of the standard curve in CSF solution was （64 ± 4） mg/L;the linear regression equation was Y=8.371 3X ＋ 6.845 7,r =0.999 1;the relative standard deviation in intra-day,inter-day and inter-week was ≤4.58%,≤ 5.38%,≤ 7.93%,respectively.The norvancomycin concentration in CSF was （43.6 ± 7.0） mg/L immediately after intravenous use of the drug,and it decreased to （22.9 ±4.2） mg/L after 1 hour,（6.5 ± 1.3） mg/L after 12 hours and （3.1 ± 0.9） mg/L after 24 hours;the drug concentration in CSF after 36 hours was lower than the value of detectable concentration in all patients.The half-life,apparent volume of distribution,area under the concentration time curve （AUC）,drug total clearance rate and 24 h renal clearance rate were （0.35 ±0.08） h,（9.9 ±2.2） L,（198 ±20） mg/L ＆#183; h,（87 ±22） ml/min and （76 ± 17） ml/min,respectively.The total efficiency was 90.0% （36/40） and no adverse reactions occurred.Linear regression analysis showed that AUC and drug total clearance rate were the main influence factors of clinical curative effect （OR =1.893,2.154;P 〈 0.05）.Conclusion The pharmacokinetic parameters of vancomycin in CSF are related to clinical efficacy;pharmacokinetic monitoring of vancomycin concentration in CSF should be applied to guild the adjustment of dosage regimen to improve the prognosis.

关 键 词：盐酸去甲万古霉素 脑脊液 药动学 临床疗效 相关性 

分 类 号：R917[医药卫生—药物分析学]