癫痫患儿丙戊酸首次给药剂量的随机对照研究  

A randomized controlled trial of initial Valproic acid dosage in epileptic children

作　　者：杨圣海 张仲斌[1] 刘明[1] 王颖慧[1] 王云秀[1] 王丽[1] 赵维[2] 吴晔 Yang Shenghai;Zhang Zhong-bin;Liu Ming;Wang Yinghui;Wang Yunxiu;Wang Li;Zhao Wet;Wu Ye(Department of Pediatrics, Peking University First Hospital, Beijing 100034, China;Department of Clinical Pharmacy, Qianfoshan Hospital Affiliated to Shandong University, Ji＇nan 250014, China)

机构地区：[1]北京大学第一医院儿科,100034 [2]山东大学附属千佛山医院药学部,济南250014 [3]首都儿科研究所附属儿童医院

出　　处：《中华实用儿科临床杂志》2018年第12期905-908,共4页Chinese Journal of Applied Clinical Pediatrics

摘　　要：目的探讨利用群体药代动力学（PPK）模型是否可以优化癫痫患儿个体化丙戊酸（VPA）初始给药剂量。方法以2015年10月至2017年5月在北京大学第一医院儿科新服用VPA治疗的癫痫患儿为研究对象，通过区组化随机分组，将入组患儿随机分为经验给药组和PPK模型给药组，经验给药组VPA首次给药剂量的确定采用20～25 mg/（kg·d），PPK模型给药组基于PPK模型确定VPA首次给药剂量。采用前瞻性随机对照研究分析比较2种方法给药后VPA血药质量浓度达到参考范围（50～100 mg/L）患儿的百分比是否存在差异。结果经验给药组共入组32例患儿，完成研究者27例；PPK模型组共入组33例患儿，完成研究者29例。经验组27例患儿癫痫发作形式包括12例局限性发作和15例全面性发作，PPK模型组29例患儿癫痫发作形式包括12例局限性发作和17例全面性发作。经验给药组患儿27例中9例为VPA添加治疗，PPK模型组29例中15例为VPA添加治疗。经验给药组VPA稳态谷质量浓度〈50 mg/L、50～100 mg/L及〉100 mg/L患儿分别为5例、21例和1例。PPK模型组实测VPA稳态谷质量浓度〈50 mg/L、50～100 mg/L及〉100 mg/L患儿分别为9例、20例和0例。经验给药组及PPK模型组VPA稳态谷质量浓度在参考范围（50～100 mg/L）患儿百分比分别为77.8%（21/27例）和69.0%（20/29例），2组比较差异无统计学意义（P〉0.05）。结论本研究并未能证实PPK模型对于VPA初始剂量的确定更具优势，但对于经验给药后不能达到参考血药质量浓度范围且临床仍有发作或临床下电发作的患儿个体化剂量调整，很可能具有更好的应用价值。ObjectiveTo investigate whether the population pharmacokinetics （PPK） models can optimize the initial dosage of individualized Valproic acid （VPA） in children with epilepsy.MethodsThe epileptic children without taking VPA previously were recruited from October 2015 to May 2017 at the Department of Pediatrics, Peking University First Hospital, and they were divided into the PPK model group and the traditional empirical method group by randomized method.The initial VPA dosages for the PPK model group were calculated by PPK model, whereas those of the traditional empirical method group were dosed at 20-25 mg/（kg·d） regularly.The steady-state serum trough concentrations of VPA were extracted, and then the number and percentage of the patients whose serum trough concentrations of VPA were 50-100 mg/L in the 2 groups were analyzed and compared with prospectively randomized me-thod.ResultsTotally 65 epileptic children were recruited and they were randomly divided into the traditional empirical method group （32 cases） and the PPK model group （33 cases）. Twenty-seven children in the traditional empirical method group were observed, and 12 children had local epilepsy attack and 15 had generalized seizures; whereas among 29 cases in the PPK model group, there were 12 local attack of epilepsy and 17 had generalized seizures.VPA add-on therapy was administrated in 9 cases and 15 cases in the traditional empirical method group and the PPK model group, respectively.There were 5 cases, 21 cases and 1 case with VPA serum concentrations of 〈50 mg/L, 50-100 mg/L and 〉100 mg/L in the traditional empirical group; while there were 9 cases, 20 cases and 0 case in the PPK model group.The VPA serum concentrations of 21 cases （77.8%, 21/27 cases） in the traditional empirical method group and 20 cases （69.0%, 20/29 cases） in the PPK model group were 50-100 mg/L, respectively, and the difference was not statistically significant（P〉0.05）.ConclusionAlthough the study doesn′t suggest that the establishe

关 键 词：儿童 癫痫 丙戊酸 群体药代动力学 随机对照研究 

分 类 号：R742.1[医药卫生—神经病学与精神病学]