Perucca E
Department of Internal Medicine and Therapeutics, University of Pavia, Italy.
Seizure. 1995 Jun;4(2):139-43. doi: 10.1016/s1059-1311(95)80094-8.
Rational prescribing of anti-epilepsy drugs in children may be complicated by a number of problems, which include: (i) difficulties in arriving rapidly at a syndromic diagnosis, at least in some cases, with consequent uncertainties about therapeutic management; (ii) difficulties in evaluating drug response in young age groups, particularly with respect to subjective side-effects affecting cognitive function; (iii) the vulnerability of infants and children to specific aspects of drug toxicity, such as liver damage induced by valproic acid or behavioural disorders caused by barbiturates; and (iv) the need to adjust dosage to account for age-dependent pharmacokinetic changes. In particular, it is known that the rate of drug metabolism changes markedly during development. Metabolic drug elimination is often reduced at birth, but drug metabolizing enzymes mature rapidly and biotransformation in infants and children usually occurs at a faster rate than in adults. The elimination of drug which are excreted unchanged in urine appears to be less influenced by age in paediatric patients, though impairment in renal drug clearance may be seen in newborns. Monitoring of serum drug concentrations may be helpful for dosage adjustments, but it is not a substitute for careful clinical observation.
儿童抗癫痫药物的合理处方可能会因一些问题而变得复杂，这些问题包括：（i）至少在某些情况下难以迅速做出综合征诊断，从而导致治疗管理存在不确定性；（ii）难以评估幼儿群体的药物反应，尤其是关于影响认知功能的主观副作用方面；（iii）婴幼儿对药物毒性的特定方面较为敏感，如丙戊酸引起的肝损伤或巴比妥类药物导致的行为障碍；以及（iv）需要根据年龄相关的药代动力学变化调整剂量。特别是，已知药物代谢速率在发育过程中会发生显著变化。出生时药物代谢消除通常会降低，但药物代谢酶会迅速成熟，婴幼儿和儿童的生物转化通常比成年人更快。在儿科患者中，经尿液原样排泄的药物消除似乎受年龄影响较小，不过新生儿可能会出现肾脏药物清除受损的情况。监测血清药物浓度可能有助于调整剂量，但它不能替代仔细的临床观察。
