维吾尔族、汉族癫痫患儿左乙拉西坦血药浓度与疗效及安全性的相关性研究

Correlation Study on Plasma Concentration of Levetiracetam with Clinical Efficacy and Safety in Xinjiang Uygur and Han Nationality Pediatric Patients with Epilepsy

关键词:  维吾尔族  汉族  癫痫  左乙拉西坦  血药浓度

Key words:  Uygur nationality  Han nationality  epilepsy  levetiracetam  plasma concentration

摘要:

目的 研究新疆维吾尔族、汉族癫痫患儿左乙拉西坦（levetiracetam，LEV）血药浓度与临床疗效及安全性之间的相关性及差异性，同时预测可获得最佳疗效的LEV稳态谷浓度（steady valley concentration，Css）。方法 采用UPLC测定300例口服LEV的癫痫患儿的Css，分析族别对LEV Css的影响；观察其疗效和不良反应，并运用Logistic回归和受试者操作特征（receiver operating characteristic curve，ROC）曲线分析维吾尔族、汉族癫痫患儿血药浓度与疗效的关系。结果 LEV的浓度剂量比（concentration-dose ratio，CDR）结果显示其在维吾尔族、汉族患儿之间的差异均无统计学意义。2组患儿在0~4岁年龄组的CDR值差异有统计学意义（P<0.05）。2组患儿的LEV给药剂量和血药浓度均呈正相关，其中维吾尔族患儿组的相关性（r=0.628，P<0.01）优于汉族患儿组（r=0.545，P<0.01）。2组患儿LEV治疗有效率分别为78.43%，81.63%。2组患儿LEV治疗有效组与无效组的LEV Css差异均具有统计学意义（P<0.05）。Logistic回归分析发现在一定浓度范围（4.07~30.88 mg·L^-1）内，2组患儿LEV Css与疗效呈正相关。2组患儿中Css对于疗效的预判准确性均强于给药剂量。当维吾尔族患儿Css ≥ 13.15 mg·L^-1和汉族患儿Css ≥ 9.28 mg·L^-1时，其临床疗效均可得到更好的保证。结论 新疆维吾尔族、汉族癫痫患儿LEV血药浓度和临床疗效及安全性之间既存在相关性又存在不同程度的差异性，通过监测LEV Css可以提高临床疗效、避免不良反应，并为新疆癫痫患儿制订个体化给药方案提供参考。

Abstract:

OBJECTIVE To study correlation and differential on the concentration of levetiracetam(LEV) with clinical efficacy and safety in Xinjiang Uygur and Han nationality pediatric patients with epilepsy, meanwhile predicted the LEV steady valley concentration(Css) that can obtain the best curative effect. METHODS Using UPLC to measure LEV Css of 300 cases pediatric patients with epilepsy, analysed the influence of race on LEV Css, and observed its curative effect and adverse reactions. Analysed the relationship between clinical efficacy and plasma concentration by using Logistic regression and subjects operating characteristics(ROC) curve. RESULTS There was no statistically significant difference between the concentration-dose ratio(CDR) results of LEV in Xinjiang Uygur and Han nationality pediatric patients. There were statistically significant differences in CDR values between the two groups in the age group of 0-4 years(P<0.05). Correlation of the LEV dosage and plasma concentration in the two groups all showed positive, the correlation of the Uygur pediatric patients group(r=0.628, P<0.01) was better than the Han nationality pediatric patients group(r=0.545, P<0.01). The effective rate of LEV treatment in the two groups was 78.43% and 81.63%. There were statistically significant differences of the LEV Css in the effective group and the ineffective group(P<0.05). There was a positive correlation between the two groups of the LEV Css in a range of concentrations (3.41-34.56 mg·L^-1) by Logistic regression analysis. The predicted accuracy of Css for curative effect was exceed than dosage in the two groups. The clinical efficacy could be better assured when the Uygur nationality pediatric patients's Css was ≥ 13.15 mg·L^-1 and the Han nationality pediatric patients's Css was ≥ 9.28 mg·L^-1. CONCLUSION There are both correlations and differential with different degrees between the plasma concentration of LEV with clinical efficacy and safety in Xinjiang Uygur and Han nationality pediatric patients with epilepsy. The clinical efficacy and adverse reactions can be improved by monitoring LEV Css, and provide the basis for the formulation of individualized drug administration program for the pediatric patients with epilepsy in Xinjiang.