Jacqz-Aigrain Evelyne, Anderson Brian J
Department of Paediatric Pharmacology, Robert Debré Hospital, 48 Boulevard Sérurier, 75019 Paris, France.
Semin Fetal Neonatal Med. 2006 Aug;11(4):251-9. doi: 10.1016/j.siny.2006.02.009. Epub 2006 May 5.
The non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen (paracetamol) are the most common analgesic drugs used in neonates and infants despite limited pharmacodynamic data. Both drugs act through inhibition of cyclooxygenase enzymes. Neonatal acetaminophen clearance is reduced in premature neonates (0.7 L h(-1) x 70 kg(-1)) and increases to 5 L h(-1) x 70 kg(-1) at term (40% adult rates); adult rates are reached within the first year of life; NSAID clearance follows similar trends. Volume of distribution is increased in the neonatal period. Dosing of both drug groups is tempered by concerns about toxicity. Acetaminophen hepatotoxicity is less common in neonates than in older children and adults, possibly due to reduced oxidative enzyme activity (e.g. CYP 2E1). Data concerning NSAID adverse effects in the neonatal period are few. Renal function is reduced 20% after NSAID use for patent ductus arteriosus closure in premature neonates and there is no increased frequency of intraventricular haemorrhage. No significant difference in the change in cerebral blood volume, change in cerebral blood flow, or tissue oxygenation index was found between administration of ibuprofen or placebo in neonates. Future studies should define concentration-response relationships for these drugs that are age and pathology specific.
尽管药效学数据有限，但非甾体抗炎药（NSAIDs）和对乙酰氨基酚（扑热息痛）仍是新生儿和婴儿最常用的镇痛药。这两种药物均通过抑制环氧化酶发挥作用。早产儿的新生儿期对乙酰氨基酚清除率降低（0.7 L h⁻¹×70 kg⁻¹），足月时增至5 L h⁻¹×70 kg⁻¹（为成人速率的40%）；在出生后第一年内达到成人速率；NSAIDs的清除率也呈现类似趋势。新生儿期分布容积增加。这两类药物的给药都因担心毒性而受到限制。新生儿期对乙酰氨基酚肝毒性比大龄儿童和成人少见，可能是由于氧化酶活性降低（如CYP 2E1）。关于NSAIDs在新生儿期不良反应的数据很少。在早产儿中，使用NSAIDs关闭动脉导管后肾功能降低20%，且脑室内出血频率未增加。在新生儿中，给予布洛芬或安慰剂后，脑血容量变化、脑血流变化或组织氧合指数均未发现显著差异。未来的研究应确定这些药物针对年龄和病理情况的浓度-反应关系。
