左乙拉西坦血药浓度影响因素探讨及参考区间的初步建立

Reference range of levetiracetam plasma concentration and its influencing factors in our hospital

目的建立癫痫患儿左乙拉西坦血药浓度的参考区间,并探讨血药浓度相关的影响因素,为临床个体化用药提供参考。方法收集规律服用左乙拉西坦不少于3个月的0~14岁门诊及住院的332例患儿血样,用高效液相色谱串联质谱(HPLC-MS/MS)法测定左乙拉西坦的血药浓度,分析单用药组、联合用药组及不同性别对左乙拉西坦血药浓度的影响。结果血药浓度数据分析显示,单用药组与联合用药组的左乙拉西坦血药浓度差异无统计学意义(P>0.05)。单用药组男性血药浓度为9.40(5.90~12.50)μg·mL^(-1),女性为7.73(5.59~10.42)μg·mL^(-1);联合用药组男性血药浓度为9.57(6.82~12.90)μg·ml-1,女性为7.62(5.84~10.40)μg·mL^(-1);总用药组男性血药浓度为9.06(5.22~12.40)μg·mL^(-1),女性为7.73(5.41~11.20)μg·mL^(-1),单用药组与总用药组不同性别间血药浓度差异均有统计学意义(均P<0.05)。本研究总样本左乙拉西坦血药浓度参考区间为2.5~24μg·mL^(-1)。结论儿童抗癫痫治疗时血药浓度与剂量存在相关性;而性别及联合用药等因素的影响,后续还需扩大样本量进一步研究验证。

Objective To establish the reference range for plasma con- centration of levetiracetam in children with epilepsy in our hospital and investigate associated factors, so as to provide the theoretical basis for the clinical personalized medication. Methods A total of 332 blood samples were collected from both outpatient and hospitalized children aged 0 - 14 years old,who took regular dosage levetiracetam for more than 3 months. Then use high performance liquid chromatography- tandem mass spectrometry （HPLC - MS/MS ） to determine the plasma concentration of levetiracetam. The influencing factors between single medication group, combined medication group and different gender were analyzed. Results There was no significant statistical difference in plasma concentration of levetiracetam between the single medication group and combination medication group （P 〉 0. 05）. The plasma concentration of male and female in single medication group were 9.40 （ 5.90 - 12. 50 ）, 7.73 （5.59 - 10. 42） μg·m L-1, while the male and female plasma concentration in combined medication group were 9.57 （6.82 - 12. 90 ）, 7.62 （5.84 - 10. 40）μg·m L-1. The male and female plasma concentration in total medication group were 9. 06（5.22 - 12.40）, 7.73（5.41 - 11.20）μg·m L-1. There was significant difference at different gender in signal medication group and combination medication group （ all P 〈 0. 05 ）. Levetiracetam plasma concentration reference range established in this study was 2. 5 -24μg·m L-1. Conclusion Plasma concentration is associated with dosage, and other factors such as sex and drug combination etc. still need further investigation.