儿童结核患者抗结核药物血药浓度影响因素及其安全性分析

Analysis of Influencing Factors and Security on the Plasma Concentration of Anti-tuberculosis Drugs in Children

关键词:  儿童  抗结核药物  血药浓度监测  安全性分析

Key words:  children  anti-tuberculosis drugs  therapeutic drug monitoring  security analysis

摘要:

目的 监测儿童结核患者抗结核药物的血药浓度，探讨血药浓度影响因素，并评价其安全性，指导临床合理用药。方法 回顾性分析浙江省中西医结合医院40例儿童结核患者接受异烟肼、利福平、吡嗪酰胺、乙胺丁醇治疗后的血药浓度监测结果、不良反应以及药物使用前后各生化指标变化情况。结果 儿童结核患者中异烟肼、利福平、吡嗪酰胺、乙胺丁醇的血药浓度达标率分别为48.15%、34.88%、73.81%、18.52%。其中，日剂量与异烟肼(P=0.0250)和利福平(P=0.0212)浓度呈正相关；年龄也是影响异烟肼(P=0.0430)和利福平(P=0.0057)浓度的因素之一，血清白蛋白(P=0.0475)和性别(P=0.0087)分别与利福平和吡嗪酰胺血药浓度相关。药物不良反应主要表现为肝功能异常(5/40，12.50%)和皮疹(4/40，10%)，抗结核药物治疗前后谷草转氨酶(aspartate aminotransferase，AST)、谷丙转氨酶(alanine aminotransferase，ALT)、尿酸水平有所升高。结论 异烟肼、利福平、乙胺丁醇在儿童结核患者中的血药浓度达标率较低，患儿抗结核治疗可能与AST、ALT、尿酸升高相关。在抗结核治疗期间进行血药浓度和肝肾功能监测有助于提高药物治疗安全性和实施个体化治疗。

Abstract:

OBJECTIVE To monitor plasma concentration of anti-tuberculosis drugs in children, and explore the influencing factors and safety of anti-tuberculosis drugs, and promote the rational use of drugs. METHODS The plasma drug concentration monitoring results of isoniazid, rifampicin, pyrazinamide and ethambutol, the adverse drug reactions and the changes of various parameters before and after treatment in 40 children with tuberculosis were analyzed retrospectively in Zhejiang Hospital of Integrated Tradtional Chinese and Western Medicine. RESULTS The compliance rates of plasma drug concentration of isoniazid, rifampicin, pyrazinamide and ethambutol in chlidren with tuberculosis were 48.15%, 34.88%, 73.81%, 18.52%, respectively. Isoniazid(P=0.0250), rifampicin(P=0.0212) concentrations were positively correlated with daily dose. Age was also one of the factors affecting the concentrations of isoniazid(P=0.0430) and rifampicin(P=0.0057). Serum albumin(P=0.0475) and sex(P=0.0087) were correlated with rifampicin and pyrazinamide, respectively. Abnormal liver function(5/40, 12.50%) and rash(4/40, 10%) were the most common adverse drug reaction. Aspartate aminotransferase(AST), alanine aminotransferase(ALT) and uric acid levels increased after treatment with anti-tuberculosis drugs. CONCLUSION The plasma drug concentrations of isoniazid, rifampicin and ethambutol in children are low. The anti-tuberculosis drugs maybe related to the increase of AST, ALT and uric acid. Therefore, monitoring of serum drug concentration, renal fuction and liver function during anti-tuberculosis treatment is helpful to improve drug safety and implement individualized treatment.