Dodson W E
Washington University School of Medicine, St. Louis, Missouri.
Epilepsia. 1988;29 Suppl 3:S10-4. doi: 10.1111/j.1528-1157.1988.tb05804.x.
About 75% of patients with epilepsy have seizures during childhood, often requiring antiepileptic therapy. Children possess all the drug-specific pharmacokinetic features of adults (e.g., nonlinearity of phenytoin elimination and autoinduction of carbamazepine metabolism), plus other factors (e.g., age, intercurrent illness, comedication) that influence dosage. Kinetic differences are maximal in newborns and infants, with limited drug elimination in premature and full-term babies, soon followed by accelerated elimination during infancy and childhood, before lower adult elimination rates develop during late childhood or early adolescence. Most children with epilepsy require two- to fourfold larger doses relative to bodyweight than adults, to achieve comparable drug levels and therapeutic effects. Although rapid growth may require increased dosage, the need is limited as relative clearance declines with age. Children of any age, but particularly premature and newborn babies, show greater individual variability in drug handling and therefore in dose requirements than adults. Clinical response and antiepileptic drug concentrations should both be monitored carefully in children.
约75%的癫痫患者在儿童期会发作，常常需要抗癫痫治疗。儿童具备成人所有特定药物的药代动力学特征（例如，苯妥英消除的非线性及卡马西平代谢的自身诱导），再加上其他影响剂量的因素（例如，年龄、并发疾病、合并用药）。新生儿和婴儿的动力学差异最大，早产儿和足月儿的药物消除有限，随后在婴儿期和儿童期消除加快，到儿童晚期或青春期早期才降至较低的成人消除率。相对于体重，大多数癫痫儿童所需剂量比成人大两到四倍，才能达到相当的药物水平和治疗效果。尽管快速生长可能需要增加剂量，但随着相对清除率随年龄下降，这种需求是有限的。任何年龄的儿童，尤其是早产儿和新生儿，在药物处理以及因此在剂量需求方面，比成人表现出更大的个体差异。儿童的临床反应和抗癫痫药物浓度都应仔细监测。
