PharmGKB summary: fluoropyrimidine pathways.
PharmGKB summary: fluoropyrimidine pathways.
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DOI：
10.1097/fpc.0b013e32833c6107
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发表时间：
2011-04
影响因子：
2.6
通讯作者：
Altman RB
中科院分区：
文献类型：
--
作者：
Thorn CF;Marsh S;Carrillo MW;McLeod HL;Klein TE;Altman RB
卡马西平（CBZ）是一种二苯并氮杂卓，是一种三环化合物，用于治疗癫痫、三叉神经痛和精神情绪障碍[1]。CBZ已报告严重不良事件，包括史蒂文斯-约翰逊综合征（SJS）、中毒性表皮坏死松解症（TEN）以及伴有嗜酸性粒细胞增多和全身症状的药物反应[2，3]。其他类型的超敏反应也与CBZ相关，包括轻度皮疹、发热、嗜酸性粒细胞增多和与其他抗惊厥药的交叉反应。高达80%对CBZ药物有特发性药物反应的患者也会对其他抗惊厥药物产生不良反应，进一步限制了治疗选择[4]。除了不良事件，缺乏疗效也可能是一个问题，多达30%的癫痫患者经历耐药性[5，6]。尽管几种候选药物基因与CBZ治疗反应相关，但这些事件发生的机制尚不完全清楚。目前的个体化治疗方法包括治疗药物监测、治疗后患者样本中药物代谢产物的测量以及随后的剂量调整。尽管这提供了药物反应表型的准确视图，但仍然存在不良事件和交叉敏感性的风险。识别将从CBZ中受益的患者，而不是遭受不良事件并在治疗前确定剂量的能力将是一个非常有价值的临床工具。在这里，我们介绍了CBZ药物基因组学（PGx）的现有知识，作为CBZ药代动力学的基因中心观点（图1），并整理了与CBZ反应相关的基因变异。
Carbamazepine (CBZ), a dibenzazepine, is a tricyclic compound used in the treatment of epilepsy, trigeminal neuralgia, and psychiatric mood disorders [1]. Serious adverse events have been reported for CBZ including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and Drug Reaction with Eosinophilia and Systemic Symptoms [2, 3]. Other types of hypersensitivity reactions are also associated with CBZ including mild skin rashes, fever, eosinophilia, and cross-reactions to other anticonvulsants. Up to 80% of patients who have an idiopathic drug reaction to CBZ drugs will also have an adverse reaction to other anticonvulsants, further restricting treatment options [4]. In addition to adverse events, lack of efficacy can also be a problem, with as many as 30% of patients with epilepsy experiencing drugresistance [5, 6]. The mechanisms by which these events occur are not entirely clear although several candidate pharmacogenes have been associated with CBZ treatment responses. Current methods to individualize treatment involve therapeutic drug monitoring, the measurement of drug metabolites in patient samples posttreatment, and subsequent dose adjustment. Although this provides an accurate view of the drug-response phenotype, it still risks adverse events and cross-sensitivity. The ability to identify the patients that will benefit from CBZ, not suffer adverse events and define dose before treatment would be a highly valuable clinical tool. Here we present the current knowledge of CBZ pharmacogenomics (PGx) as a gene centered view of the pharmacokinetics of CBZ (Fig. 1) and collate the gene variants associated with CBZ responses.