Dannelley Jennifer F, Martin Erin M, Chaaban Hala, Miller Jamie L
Section of Pulmonology and Cystic Fibrosis, Department of Pediatrics, University of Oklahoma College of Medicine, Oklahoma City, Oklahoma.
Department of Pharmacy, University of Missouri Healthcare, Columbia, Missouri.
Am J Perinatol. 2017 Jul;34(9):833-838. doi: 10.1055/s-0037-1599822. Epub 2017 Mar 8.
Metronidazole dosing recommendations vary significantly for premature infants in pediatric dosing references and can result in confusion for prescribers. We performed a literature search identifying articles evaluating the pharmacokinetics and dosing of metronidazole in premature infants. The search was limited to English-language articles in MEDLINE (January 1946 to December 2016), EMBASE (January 1974 to December 2016), and (January 1970 to December 2016). Reference citations from relevant articles were also reviewed. Six pharmacokinetic studies, representing 152 neonates, were included; however, only three of the well-defined studies were reviewed in depth, and the other three studies were considered foundational. The pharmacokinetic studies included in this review indicate that some published dosing recommendations in pediatric dosing references may result in subtherapeutic metronidazole concentrations. Therefore, postmenstrual age based dosing recommendations were provided by the authors of these pharmacokinetic studies based on a pharmacodynamic target of 6 to 8 mg/L; yet, these dosing recommendations differ from one another. The pharmacokinetic studies included in this review provide some guidance to dosing; however, a major limitation is that outcomes of clinical efficacy and safety were not evaluated. Future studies targeting the optimal dosing and serum concentrations required for clinical efficacy are needed.
甲硝唑的给药建议在儿科用药参考中对于早产儿有显著差异，这可能会给开处方的医生带来困惑。我们进行了文献检索，以找出评估甲硝唑在早产儿体内药代动力学和给药剂量的文章。检索仅限于MEDLINE（1946年1月至2016年12月）、EMBASE（1974年1月至2016年12月）以及（1970年1月至2016年12月）中的英文文章。还对相关文章的参考文献进行了审查。纳入了六项药代动力学研究，涉及152名新生儿；然而，仅对其中三项定义明确的研究进行了深入审查，另外三项研究被视为基础研究。本综述中纳入的药代动力学研究表明，儿科用药参考中一些已发表的给药建议可能导致甲硝唑浓度低于治疗水平。因此，这些药代动力学研究的作者基于6至8毫克/升的药效学目标提供了基于月经后年龄的给药建议；然而，这些给药建议彼此不同。本综述中纳入的药代动力学研究为给药提供了一些指导；然而，一个主要限制是未评估临床疗效和安全性的结果。需要针对临床疗效所需的最佳给药剂量和血清浓度开展未来研究。
