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《芬太尼及其衍生物在儿童中的药代动力学:综述》勘误

Correction to: Pharmacokinetics of Fentanyl and Its Derivatives in Children: A Comprehensive Review.

作者信息

Ziesenitz Victoria C, Vaughns Janelle D, Koch Gilbert, Mikus Gerd, van den Anker Johannes N

机构信息

Division of Pediatric Pharmacology and Pharmacometrics, University of Basel Children's Hospital, Spitalstrasse 33, 4056, Basel, Switzerland.

Department of Pediatric Cardiology, University Children's Hospital, Heidelberg, Germany.

出版信息

Clin Pharmacokinet. 2018 Mar;57(3):393-417. doi: 10.1007/s40262-017-0609-2.

Abstract

Fentanyl and its derivatives sufentanil, alfentanil, and remifentanil are potent opioids. A comprehensive review of the use of fentanyl and its derivatives in the pediatric population was performed using the National Library of Medicine PubMed. Studies were included if they contained original pharmacokinetic parameters or models using established routes of administration in patients younger than 18 years of age. Of 372 retrieved articles, 44 eligible pharmacokinetic studies contained data of 821 patients younger than 18 years of age, including more than 46 preterm infants, 64 full-term neonates, 115 infants/toddlers, 188 children, and 28 adolescents. Underlying diagnoses included congenital heart and pulmonary disease and abdominal disorders. Routes of drug administration were intravenous, epidural, oral-transmucosal, intranasal, and transdermal. Despite extensive use in daily clinical practice, few studies have been performed. Preterm and term infants have lower clearance and protein binding. Pharmacokinetics was not altered by chronic renal or hepatic disease. Analyses of the pooled individual patients' data revealed that clearance maturation relating to body weight could be best described by the Hill function for sufentanil (R  = 0.71, B 876 mL/min, K 16.3 kg) and alfentanil (R  = 0.70, B 420 mL/min, K 28 kg). The allometric exponent for estimation of clearance of sufentanil was 0.99 and 0.75 for alfentanil clearance. Maturation of remifentanil clearance was described by linear regression to bodyweight (R  = 0.69). The allometric exponent for estimation of remifentanil clearance was 0.76. For fentanyl, linear regression showed only a weak correlation between clearance and bodyweight in preterm and term neonates (R  = 0.22) owing to a lack of data in older age groups. A large heterogeneity regarding study design, clinical setting, drug administration, laboratory assays, and pharmacokinetic estimation was observed between studies introducing bias into the analyses performed in this review. A limitation of this review is that pharmacokinetic data, based on different modes of administration, dosing schemes, and parameter estimation methods, were combined.

摘要

芬太尼及其衍生物舒芬太尼、阿芬太尼和瑞芬太尼都是强效阿片类药物。我们使用美国国立医学图书馆的PubMed数据库对芬太尼及其衍生物在儿科人群中的应用进行了全面综述。如果研究包含18岁以下患者使用既定给药途径的原始药代动力学参数或模型,则纳入研究。在检索到的372篇文章中,44项符合条件的药代动力学研究包含了821名18岁以下患者的数据,其中包括46名以上早产儿、64名足月儿、115名婴儿/幼儿、188名儿童和28名青少年。潜在诊断包括先天性心脏病、肺部疾病和腹部疾病。给药途径包括静脉内、硬膜外、口腔黏膜、鼻内和透皮。尽管在日常临床实践中广泛使用,但相关研究却很少。早产儿和足月儿的清除率和蛋白结合率较低。慢性肾脏或肝脏疾病不会改变药代动力学。对汇总的个体患者数据进行分析后发现,与体重相关的清除率成熟情况,对于舒芬太尼(R = 0.71,B = 876 mL/min,K = 16.3 kg)和阿芬太尼(R = 0.70,B = 420 mL/min,K = 28 kg)而言,用希尔函数描述最为合适。舒芬太尼清除率估计的异速生长指数为0.99,阿芬太尼清除率的异速生长指数为0.75。瑞芬太尼清除率的成熟情况通过与体重的线性回归来描述(R = 0.69)。瑞芬太尼清除率估计的异速生长指数为0.76。对于芬太尼,由于老年组数据不足,线性回归显示早产儿和足月儿的清除率与体重之间仅存在微弱相关性(R = 0.22)。在研究设计、临床环境、药物给药、实验室检测和药代动力学估计方面,各研究之间存在很大异质性,这给本综述中的分析带来了偏差。本综述的一个局限性在于,基于不同给药方式、给药方案和参数估计方法的药代动力学数据被合并在一起。

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