Djordjevic Natasa, Jankovic Slobodan M, Milovanovic Jasmina R
Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica Street, 69, 34000, Kragujevac, Serbia.
Eur J Drug Metab Pharmacokinet. 2017 Oct;42(5):729-744. doi: 10.1007/s13318-016-0397-3.
Although carbamazepine is one of the oldest anticonvulsant drugs, it is still heavily utilized for treatment of epilepsy in children. The aim of this article was to review the current knowledge about pharmacokinetics and pharmacogenetics of carbamazepine in children. The literature for this review was systematically searched for in the MEDLINE and SCINDEKS databases. Oral bioavailability of carbamazepine in children is about 75-85%, and it is approximately 75-85% bound to plasma proteins. Apparent volume of distribution is 1.2-1.9 l/kg and total clearance between 0.05 and 0.1 l/h/kg. Pharmacokinetics of carbamazepine in children is age and body weight dependent and highly variable due to influence of dosing regimen and co-medication. The current evidence on the importance of pharmacogenetics for carbamazepine efficacy and safety in children supports the association of PXR1B, HNF4a rs2071197, CYP1A21F, ABCC2 1249G>A, and PRRT2 c.649dupC with either pharmacokinetics or pharmacodynamics of carbamazepine. The importance of human leukocyte antigen (HLA) typing for prediction of adverse drug reactions to carbamazepine in children is also confirmed. Both genetic and environmental factors are responsible for shaping pharmacokinetics and pharmacodynamics of carbamazepine in children. To ensure safe and effective use of carbamazepine in this population, physicians should adjust dosing regimen according to existing pattern of genetic and environmental influences.
尽管卡马西平是最古老的抗惊厥药物之一，但它仍被大量用于治疗儿童癫痫。本文的目的是综述目前关于卡马西平在儿童体内的药代动力学和药物遗传学的知识。本综述的文献在MEDLINE和SCINDEKS数据库中进行了系统检索。卡马西平在儿童中的口服生物利用度约为75 - 85%，与血浆蛋白的结合率约为75 - 85%。表观分布容积为1.2 - 1.9 l/kg，总清除率在0.05至0.1 l/h/kg之间。卡马西平在儿童中的药代动力学取决于年龄和体重，并且由于给药方案和联合用药的影响而具有高度变异性。目前关于药物遗传学对卡马西平在儿童中的疗效和安全性重要性的证据支持PXR1B、HNF4a rs2071197、CYP1A21F、ABCC2 1249G>A和PRRT2 c.649dupC与卡马西平的药代动力学或药效动力学之间的关联。人类白细胞抗原（HLA）分型对预测儿童卡马西平药物不良反应的重要性也得到了证实。遗传和环境因素都对塑造卡马西平在儿童中的药代动力学和药效动力学起作用。为确保在该人群中安全有效地使用卡马西平，医生应根据现有的遗传和环境影响模式调整给药方案。
