Linezolid pharmacokinetics in pediatric patients: an overview
Linezolid pharmacokinetics in pediatric patients: an overview
复制标题
DOI：
10.1097/01.inf.0000086954.43010.63
复制
发表时间：
2003-09-01
影响因子：
3.6
通讯作者：
Hopkins, NK
中科院分区：
文献类型：
--
作者：
Jungbluth, GL;Welshman, IR;Hopkins, NK
儿童和成人之间存在许多生理和发育差异，这些差异会影响药物的吸收、分布、代谢和消除。因此，确定儿童个体药物的具体药代动力学特征是非常重要的，这样才能在临床试验中制定出适合年龄的给药方案并对其进行评估。本文综述了利奈唑胺在儿科患者中的药代动力学参数以及该人群批准推荐剂量的基本原理。利奈唑胺在儿科患者中的药代动力学已经在4项临床试验中进行了评估，包括从早产儿到18岁的180例患者。在所有这些研究中，患者接受单次静脉注射利奈唑胺。血浆利奈唑胺浓度已通过高效液相色谱法（成人研究）或液相色谱/质谱/质谱法（儿童研究）测定。利奈唑胺的药代动力学，特别是消除清除率，是年龄依赖性的。12岁以下儿童的药物浓度-时间曲线下面积比成人小，清除率快，消除半衰期短。虽然新生儿的清除率与成人相似，但在生命的第一周内清除率迅速增加，到生命的第七天，清除率比成人高2- 3倍。利奈唑胺的清除率在幼儿中逐渐下降，到青春期与成人值相似。利奈唑胺在12岁及以上儿童的药代动力学与成人的药代动力学无显著差异。由于利奈唑胺具有较高的清除率和较低的药物浓度-时间曲线下面积，因此对于12岁以下的儿童来说，需要较短的给药间隔才能产生足够的药物暴露以对抗目标革兰氏阳性病原体。
There are a number of physiologic and developmental differences between children and adults that can influence the absorption, distribution, metabolism and elimination of a drug. Therefore it is important to determine the specific pharmacokinetic characteristics for individual drugs in pediatric patients so that appropriate age-specific dosage regimens can be developed and evaluated in clinical trials. This review summarizes the pharmacokinetic parameters of linezolid in pediatric patients and the rationale for the approved dosing recommendations for this population.Methods. The pharmacokinetics of linezolid in pediatric patients has been evaluated in 4 clinical trials, including >180 patients ranging in age from preterm newborn infants up to 18 years of age. In all of these studies, patients received a single intravenous dose of linezolid. Plasma linezolid concentrations have been determined by validated high performance liquid chromatography (adult studies) or liquid chromatography/ mass spectrometry/mass spectrometry (pediatric studies) methods.Results. The pharmacokinetics of linezolid, especially elimination clearance, is age-dependent. Children younger than 12 years of age have a smaller area under the drug concentration-time curve, a faster clearance and a shorter elimination half-life than adults. Although clearance rates in newborn infants are similar to those in adults, clearance increases rapidly during the first week of life, becoming 2- to 3-fold higher than in adults by the seventh day of life. The clearance of linezolid decreases gradually among young children, becoming similar to adult values by adolescence. The pharmacokinetics of linezolid in children age 12 years and older is not significantly different from that of adults.Conclusions. Because of the higher clearance and lower area under the drug concentration-time curve, a shorter dosing interval for linezolid is required for children younger than 12 years of age to produce adequate drug exposure against target Gram-positive pathogens.