Park Kyoung-Jin, Kim Jung-Ryul, Joo Eun Yeon, Seo Dae Won, Hong Seung Bong, Ko Jae-Wook, Kim Suk-Ran, Huh Wooseong, Lee Soo-Youn
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Clin Neuropharmacol. 2012 Jan-Feb;35(1):40-4. doi: 10.1097/WNF.0b013e31824150a5.
To determine first whether there was a clear relationship between concentrations of the active metabolite of oxcarbazepine (OXC), 10-hydroxycarbamazepine (OHC), and dose adjusted for weight, and second, whether the clearance of OHC was influenced by comedication with enzyme-inducing antiepileptic drugs (EIAED).
We analyzed 254 cases (patients 3-80 years of age) of OXC therapeutic drug monitoring, retrospectively. The cases were categorized into OXC monotherapy (n = 78), OXC in combination with EIAED (n = 73), and OXC in combination with non-EIAED (n = 103). The serum OHC concentrations of predose samples were measured by high-performance liquid chromatography. A population pharmacokinetic model was developed using NONMEM.
The mean ± SD serum concentration of OHC was 14.47 ± 8.28 μg/mL at a mean daily dose of 16.22 ± 7.99 mg/kg. The serum concentration of OHC was correlated with the OXC dose per body weight (r = 0.6005; P < 0.0001). No association was found between OHC concentration and patient age, weight, sex, or seizure type. The concentration-to-dose ratio on OXC in combination with EIAED was significantly lower than that on OXC monotherapy (P = 0.002) or OXC in combination with non-EIAED (P < 0.0001). In population pharmacokinetic modeling, the apparent clearance of OHC was higher by 31.2% in combination with EIAED than in other groups.
The serum concentration of OHC was statistically significantly correlated with the dose of OXC and negatively correlated with comedication of EIAED. Population pharmacokinetic analysis showed that the apparent clearance of OHC increased with comedication with EIAEDs.
首先确定奥卡西平（OXC）的活性代谢物10 - 羟基卡马西平（OHC）的浓度与体重调整剂量之间是否存在明确关系，其次确定OHC的清除率是否受酶诱导抗癫痫药物（EIAED）合并用药的影响。
我们回顾性分析了254例（年龄3至80岁）进行OXC治疗药物监测的病例。这些病例被分为OXC单药治疗组（n = 78）、OXC与EIAED联合治疗组（n = 73）以及OXC与非EIAED联合治疗组（n = 103）。通过高效液相色谱法测定给药前样本的血清OHC浓度。使用NONMEM建立群体药代动力学模型。
在平均日剂量为16.22±7.99mg/kg时，OHC的平均±标准差血清浓度为14.47±8.28μg/mL。OHC的血清浓度与每体重OXC剂量相关（r = 0.6005；P < 0.0001）。未发现OHC浓度与患者年龄、体重、性别或癫痫发作类型之间存在关联。OXC与EIAED联合使用时的浓度 - 剂量比显著低于OXC单药治疗组（P = 0.002）或OXC与非EIAED联合治疗组（P < 0.0001）。在群体药代动力学建模中，与EIAED联合使用时OHC的表观清除率比其他组高31.2%。
OHC的血清浓度与OXC剂量在统计学上显著相关，且与EIAED合并用药呈负相关。群体药代动力学分析表明，OHC的表观清除率随EIAED合并用药而增加。
