Lu Qiong, Huang Yuan-Tao, Shu Yi, Xu Ping, Xiang Da-Xiong, Qu Qiang, Qu Jian
Department of Pharmacy, the Second Xiangya Hospital Institute of Clinical Pharmacy, Central South University Department of Neurology, The Brain Hospital of Hunan Province Department of Neurology, the Second Xiangya Hospital Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China.
Medicine (Baltimore). 2018 Jul;97(30):e11662. doi: 10.1097/MD.0000000000011662.
Carbamazepine (CBZ) is a widely used antiepileptic drug with large interindividual variability in serum concentrations. Previous studies found that CYP3A53 (rs776746), UGT2B72 (802C>T), and UGT2B73 (211G>T) variants could change the enzymes' activity, which may influence drug concentrations. Our study aims to investigate whether these variants affect steady-state CBZ concentrations in Chinese epileptic patients. In our study, 62 epileptic patients who received CBZ as monotherapy were monitored for steady-state CBZ concentrations. We used polymerase chain reaction (PCR)-based Sanger sequencing to assess the variants CYP3A53, UGT2B72, and UGT2B73. The results showed a positive correlation between dose and CBZ serum concentration in all patients and in patients with 3 different variants (all P < .05). After CBZ concentrations were normalized by the dose administered, negative correlations between dose-normalized CBZ concentrations and CBZ doses were observed in all patients, and in CYP3A53 and UGT2B73 patients (all P < .05), but not in UGT2B72 patients (P = .1080). UGT2B72 patients exhibited lower dose-normalized CBZ concentrations and larger CBZ dose requirements than UGT2B71/1 patients (P = .0139, P = .032, respectively). There were no differences between UGT2B73, UGT2B71/1 and CYP3A53, and CYP3A51/*1 patients with regard to steady-state CBZ concentration, dose-normalized concentration, required CBZ dose, and body weight-normalized dose (all P > .05). Moreover, a significant difference in body weight-normalized CBZ dose between UGT2B7 GC and TT haplotype patients was observed (P = .0154). In conclusion, our study found that the UGT2B72 variant, but not the CYP3A53 or UGT2B73 variant, could affect steady-state CBZ concentrations in epileptic patients.
卡马西平（CBZ）是一种广泛使用的抗癫痫药物，其血清浓度存在较大的个体差异。先前的研究发现，CYP3A53（rs776746）、UGT2B72（802C>T）和UGT2B73（211G>T）变异可能会改变酶的活性，这可能会影响药物浓度。我们的研究旨在调查这些变异是否会影响中国癫痫患者的卡马西平稳态浓度。在我们的研究中，对62例接受卡马西平单药治疗的癫痫患者进行了卡马西平稳态浓度监测。我们使用基于聚合酶链反应（PCR）的桑格测序法来评估CYP3A53、UGT2B72和UGT2B73变异。结果显示，所有患者以及具有3种不同变异的患者中，剂量与卡马西平血清浓度之间均呈正相关（所有P<0.05）。在将卡马西平浓度按给药剂量进行标准化后，在所有患者以及CYP3A53和UGT2B73患者中观察到剂量标准化的卡马西平浓度与卡马西平剂量之间呈负相关（所有P<0.05），但在UGT2B72患者中未观察到（P=0.1080）。与UGT2B71/1患者相比，UGT2B72患者的剂量标准化卡马西平浓度较低，卡马西平剂量需求较大（分别为P=0.0139，P=0.032）。在稳态卡马西平浓度、剂量标准化浓度、所需卡马西平剂量和体重标准化剂量方面，UGT2B73、UGT2B71/1患者与CYP3A53、CYP3A51/*1患者之间无差异（所有P>0.05）。此外，观察到UGT2B7 GC和TT单倍型患者之间体重标准化卡马西平剂量存在显著差异（P=0.0154）。总之，我们的研究发现，UGT2B72变异而非CYP3A53或UGT2B73变异可影响癫痫患者的卡马西平稳态浓度。
