Objectives: Due to the narrow therapeutic window of valproic acid (VPA), grievous adverse reactions such as hepatotoxicity, nephrotoxicity may occur in patients with epilepsy for a long time. This study aimed to explore the effect of VPA concentration on biochemical and routine blood test related to liver, renal, and hematology in epileptic outpatients treated with VPA alone or combined with other antiepileptic drugs.
Methods: A total of 3 194 Chinese epileptic outpatients from Xiangya Hospital, were analyzed in a crude analysis after stratifying through dosage regimens. The plasma VPA concentration was detected by gas chromatography method and then standardized through dosage and body weight. Ten biochemical indexes related to liver, renal, and hematology were evaluated.
Results: Of all patients, blood urea nitrogen (BUN), serum creatinine (SCr) level, and erythrocyte count (RBC) showed positive correlations with standardized VPA concentration (r=0.494, r=0.157, r=0.596, respectively), while platelet specific volume (PCT) and blood platelet (PLT) showed negative correlations with standardized VPA concentration (r=-5.500, r=-0.086, respectively). After stratifying through dosage regimens, significantly positive associations between SCr and standardized VPA concentration were found in the juvenile patients from the monotherapy group and combination therapy group (r=1.800, r=0.352, respectively). In addition, PLT and leukocyte count (WBC) in the juvenile patients from the combination therapy group were negatively correlated with standardized VPA concentration (r=-1.463, r=-0.079, respectively), while RBC showed a positive association with standardized VPA concentration in the juvenile patients from the monotherapy group (r=0.068).
Conclusions: SCr level is significantly associated with plasma VPA concentration. Drug combination and age are important factors leading to hematological disorders. The finding provides potential theoretical guidance for the rational and safe clinical use of VPA.
目的: 由于丙戊酸(valproic acid，VPA)治疗窗窄，癫痫患者长期应用可能出现肝毒性、肾毒性等一系列不良反应。本研究探讨血浆VPA浓度与单用VPA或联合应用其他抗癫痫药物治疗的门诊癫痫患者肝、肾、血液生化指标的相关性。方法: 采用分层分析中南大学湘雅医院3 194例门诊癫痫患者的给药方案。采用气相色谱法测定血浆VPA浓度，并通过给药剂量与患者体重进行标准化。对10项与肝、肾、血液系统有关的临床生化指标进行评价。结果: 在所有患者中，尿素氮、血肌酐水平、红细胞计数与标准化VPA浓度呈正相关(r=0.494，r=0.157，r=0.596)，而血小板比容、血小板计数与标准化VPA浓度呈负相关(r=-5.500，r=-0.086)。通过对患者年龄或给药方案进行分层后，单药组和联合用药组的青少年患者血肌酐水平与标准化VPA浓度呈正相关(r=1.800，r=0.352)。此外，联合用药组青少年患者的血小板和白细胞计数与标准化VPA浓度呈负相关(r=-1.463，r=-0.079)，而单药治疗组青少年患者的红细胞计数与标准化VPA浓度呈正相关(r=0.068)。结论: 血肌酐水平与血浆VPA浓度显著相关，年龄及联合用药是引起血液系统指标异常的重要因素。这些发现为临床对于VPA的合理和安全应用提供了潜在的理论指导。.
Keywords: biochemical indexes; epilepsy; toxicity; valproic acid.