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新生儿期青霉素类、头孢菌素类和氨基糖苷类药物的临床药代动力学:综述

Clinical Pharmacokinetics of Penicillins, Cephalosporins and Aminoglycosides in the Neonate: A Review.

作者信息

Pacifici Gian Maria

机构信息

Section of Pharmacology, Department of Neurosciences, Medical School, University of Pisa, Via Roma 55, 56126 Pisa, Italy.

出版信息

Pharmaceuticals (Basel). 2010 Aug 12;3(8):2568-2591. doi: 10.3390/ph3082568.

Abstract

Bacterial infections are common in the neonates and are a major cause of morbidity and mortality. Sixty percent of preterm infants admitted to neonatal intensive care units received at least one antibiotic during the first week of life. Penicillins, aminoglycosides and cephalosporins comprised 53, 43 and 16%, respectively. Kinetic parameters such as the half-life (t), clearance (Cl), and volume of distribution (Vd) change with development, so the kinetics of penicillins, cephalosporins and aminoglycosides need to be studied in order to optimise therapy with these drugs. The aim of this study is to review the pharmacokinetics of penicillins, cephalosporins and aminoglycosides in the neonate in a single article in order to provide a critical analysis of the literature and thus provide a useful tool in the hands of physicians. The bibliographic search was performed electronically using PubMed, as the search engine, until February 2, 2010. Medline search terms were as follows: pharmacokinetics AND (penicillins OR cephalosporins OR aminoglycosides) AND infant, newborn, limiting to humans. Penicillins, cephalosporins and aminoglycosides are fairly water soluble and are mainly eliminated by the kidneys. The maturation of the kidneys governs the pharmacokinetics of penicillins, cephalosporins and aminoglycosides in the neonate. The renal excretory function is reduced in preterms compared to term infants and Cl of these drugs is reduced in premature infants. Gestational and postnatal ages are important factors in the maturation of the neonate and, as these ages proceed, Cl of penicillins, cephalosporins and aminoglycosides increases. Cl and t are influenced by development and this must be taken into consideration when planning a dosage regimen with these drugs. More pharmacokinetic studies are required to ensure that the dose recommended for the treatment of sepsis in the neonate is evidence based.

摘要

细菌感染在新生儿中很常见,是发病和死亡的主要原因。入住新生儿重症监护病房的早产儿中有60%在出生后第一周内至少接受过一种抗生素治疗。青霉素、氨基糖苷类和头孢菌素类药物的使用比例分别为53%、43%和16%。诸如半衰期(t)、清除率(Cl)和分布容积(Vd)等动力学参数会随着发育而变化,因此需要研究青霉素、头孢菌素类和氨基糖苷类药物的动力学,以便优化这些药物的治疗效果。本研究的目的是在一篇文章中综述新生儿中青霉素、头孢菌素类和氨基糖苷类药物的药代动力学,以便对文献进行批判性分析,从而为医生提供一个有用的工具。使用PubMed作为搜索引擎进行电子文献检索,截至2010年2月2日。Medline检索词如下:药代动力学 AND(青霉素 OR 头孢菌素类 OR 氨基糖苷类)AND 婴儿,新生儿,仅限于人类。青霉素、头孢菌素类和氨基糖苷类药物水溶性相当高,主要通过肾脏排泄。肾脏的成熟程度决定了新生儿中青霉素、头孢菌素类和氨基糖苷类药物的药代动力学。与足月儿相比,早产儿的肾脏排泄功能降低,这些药物在早产儿中的清除率也降低。胎龄和出生后年龄是新生儿成熟的重要因素,随着这些年龄的增长,青霉素、头孢菌素类和氨基糖苷类药物的清除率会增加。清除率和半衰期受发育影响,在制定这些药物的给药方案时必须考虑到这一点。需要更多的药代动力学研究来确保为新生儿败血症治疗推荐的剂量是有循证依据的。

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