Ghodrat Mandana
Emory Crawford Long Hospital, Atlanta, GA, USA.
Am J Health Syst Pharm. 2006 Aug 15;63(16):1504-21. doi: 10.2146/ajhp060002.
The pharmacology, clinical efficacy, and cost considerations of exogenous lung surfactants are reviewed.
Exogenous pulmonary surfactants, along with advancements in ventilatory care, have significantly reduced the incidence of respiratory distress syndrome (RDS) and its related complications in infants. The following exogenous surfactants are approved for the prophylaxis and treatment (rescue) of neonatal RDS: beractant, a modified natural surfactant; calfactant and poractant, both natural surfactants; and colfosceril, a synthetic surfactant that is not currently available in the United States. Lucinactant, a synthetic surfactant, is under investigation and received approvable status from the Food and Drug Administration in February 2005. The surfactants are delivered directly to their site of action, and only small amounts reach the systemic circulation. Bioavailability to the distal airways and alveoli depends on the method of delivery, the stage and severity of pulmonary disease, and the properties of the particular surfactant. According to data from clinical trials, the use of exogenous surfactant therapy for rescue within the first two hours of life appears to be as efficacious as prophylaxis in most premature infants.
Comparative trials of surfactants have proven the efficacy of both synthetic and natural surfactants in the prevention and treatment of RDS. However, these trials have universally demonstrated greater reduction in the immediate need for ventilator support in infants who receive natural surfactants. Natural preparations cause less pneumothorax, bronchopulmonary dysplasia, and mortality compared with synthetic preparations. Synthetic agents offer the potential advantages of an unlimited supply with consistent pharmaceutical quality and no risk of transmitting infectious disease or causing immunologic sensitization.
对外源性肺表面活性物质的药理学、临床疗效及成本考量进行综述。
外源性肺表面活性物质与通气护理的进展一起,已显著降低了婴儿呼吸窘迫综合征(RDS)及其相关并发症的发生率。以下外源性表面活性物质被批准用于新生儿RDS的预防和治疗(抢救):贝拉克坦,一种改良的天然表面活性物质;卡肺表面活性物质和泊肺表面活性物质,均为天然表面活性物质;以及考福斯西尔,一种合成表面活性物质,目前在美国无法获得。路西那坦,一种合成表面活性物质,正在进行研究,并于2005年2月获得美国食品药品监督管理局的可批准状态。这些表面活性物质直接输送到其作用部位,只有少量进入体循环。远端气道和肺泡的生物利用度取决于给药方法、肺部疾病的阶段和严重程度以及特定表面活性物质的特性。根据临床试验数据,对于大多数早产儿,在出生后两小时内使用外源性表面活性物质进行抢救治疗似乎与预防治疗同样有效。
表面活性物质的比较试验已证明合成和天然表面活性物质在预防和治疗RDS方面均有效。然而,这些试验普遍表明,接受天然表面活性物质的婴儿对呼吸机支持的即时需求减少得更多。与合成制剂相比,天然制剂导致的气胸、支气管肺发育不良和死亡率更低。合成制剂具有供应无限、药品质量一致、无传染病传播风险或免疫致敏风险等潜在优势。