Abstract:

Objective  To investigate the value of blood concentration monitoring of 10-monohydroxy carbamazepine (MHD), the active metabolite of oxcarbazepine (OXC), in the treatment ofchildhood focal epilepsy. Methods  A total of 110 children with focal epilepsy took OXC for 3 months and then the MHD concentrations were determined by high pressure liquid chromatography (HPLC).  Results  The average dose of OXC in 110 children was (25.52 ± 7.28) mg/(kg·d) and the valley point concentration of MHD was 7.00 (4.95, 10.50) mg/L, and 89 cases (80.91%) < 12 mg/L. A linear relationship between MHD valley point concentration and OXC dose (r_s = 0.337, P = 0.000) was shown by Spearman rank correlation analysis. The dosage of OXC for older ( > 7 years) children was significantly lower than that of younger (≤ 7 years) children [(23.13 ± 5.56) mg/(kg·d) vs. (28.09 ± 8.06) mg/(kg·d); t = 3.778, P = 0.000], while there was no significant difference between the concentration of children with different sexes (t = 1.067, P = 0.288), between children with and without drug resistant epilepsy (DRE; t = 1.417, P = 0.159) and between monotherapy and combination drug therapy (t = 1.671, P = 0.098). The MHD valley point concentration in DRE group was lower than that of non-DRE group [6.32 (3.05, 8.58) mg/L vs. 8.30 (5.75, 10.85) mg/L; Z = 2.380, P = 0.017], while there was no significant difference between the concentration of children with different sexes (Z = 0.604, P = 0.546), between older and younger children (Z = 0.179, P = 0.858) and between monotherapy and combination drug therapy (Z = 1.583, P = 0.113).  Conclusions  There is a linear relationship between MHD steady state valley point concentration and the dose of OXC. To achieve the same MHD level, the younger children need to take a larger dose of OXC. When OXC is used to treat drug resistant focal epilepsy in children, the dosage should be adjusted according to the monitoring of blood concentration of MHD.

Key words: Epilepsy, Child, Carbamazepine, Plasma concentration, Chromatography, high pressure liquid

摘要：

目的 探讨奥卡西平活性代谢产物10?单羟基卡马西平（MHD）血药浓度测定在儿童局灶性癫治疗中的应用价值。 方法 共110 例儿童局灶性癫患者于奥卡西平单药或药物联合治疗3 个月后，采用高效液相色谱法测定MHD 血药谷浓度。 结果 110 例患儿奥卡西平平均治疗剂量（25.52 ±7.28）mg/（kg·d），MHD 中位血药谷浓度7.00（4.95，10.50）mg/L，89 例（80.91%）< 12 mg/L。Spearman 秩相关分析，MHD 血药谷浓度与奥卡西平治疗剂量呈正相关（rs = 0.337，P = .000）。奥卡西平治疗剂量仅年长（> 7 岁）局灶性癫患儿低于年幼（≤ 7 岁）患儿且差异有统计学意义［（23.13 ± 5.56）mg/（kg·d）对（28.09 ± 8.06）mg/（kg·d）；t = 3.778，P = 0.000］，而男性与女性（t = 1.067，P = 0.288）、药物难治性与非药物难治性（t = 1.417，P = 0.159）、单药治疗与药物联合治疗（t = 1.671，P = 0.098）组间差异无统计学意义；MHD 血药谷浓度仅药物难治性局灶性癫患儿低于非药物难治性患儿且差异有统计学意义［6.32（3.05，8.58）mg/L 对8.30（5.75，10.85）mg/L；Z = 2.380，P = 0.017］，而男性与女性（Z = 0.604，P = 0.546）、年长与年幼（Z = 0.179，P = 0.858）、单药治疗与药物联合治疗（Z = 1.583，P = 0.113）组间差异无统计学意义。 结论 MHD 血药谷浓度与奥卡西平治疗剂量呈正相关关系；为达到相同的MHD 血药浓度，年幼局灶性癫患儿应服用更大剂量的奥卡西平；奥卡西平治疗儿童药物难治性局灶性癫时，应根据MHD血药浓度及时调整药物剂量。

关键词: 癫痫, 儿童, 卡马西平, 血药浓度, 色谱法, 高压液相