Clinical Pharmacokinetics ( IF 4.6 ) Pub Date : 2022-03-31 , DOI: 10.1007/s40262-022-01116-3 Fleur M Keij 1, 2 , Gerdien A Tramper-Stranders 1, 2 , Birgit C P Koch 3 , Irwin K M Reiss 1 , Anouk E Muller 4, 5 , René F Kornelisse 1 , Karel Allegaert 3, 6, 7
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Background and Objective
Clavulanic acid is a commonly used β-lactam inhibitor in pediatrics for a variety of infections. Clear insight into its mode of action is lacking, however, and a target has not been identified. The dosing of clavulanic acid is currently based on that of the partner drug (amoxicillin or ticarcillin). Still, proper dosing of the compound is needed because clavulanic acid has been associated with adverse effects. In this systematic review, we aim to describe the current literature on the pharmacokinetics of clavulanic acid in the pediatric population
Methods
We performed a systematic search in MEDLINE, Embase.com, Cochrane Central, Google Scholar, and Web of Science. We included all published studies reporting pharmacokinetic data on clavulanic acid in neonates and children 0–18 years of age.
Results
The search resulted in 18 original studies that met the inclusion criteria. In general, the variation in drug exposure was large, which can be partly explained by differences in disease state, route of administration, or age. Unfortunately, the studies’ limited background information hampered in-depth assessment of the observed variability.
Conclusion
The pharmacokinetics of clavulanic acid in pediatric patients is highly variable, similar to reports in adults, but more pronounced. Significant knowledge gaps remain with regard to the population-specific explanation for this variability. Model-based pharmacokinetic studies that address both maturational and disease-specific changes in the pediatric population are therefore needed. Furthermore, additional pharmacodynamic studies are needed to define a clear target. The combined outcomes will eventually lead to pharmacokinetic-pharmacodynamic modeling of clavulanic acid and targeted exposure.
Clinical Trial Registration
PROSPERO CRD42020137253.
中文翻译：
克拉维酸在儿科人群中的药代动力学：系统文献综述
背景与目的
克拉维酸是儿科常用的β-内酰胺抑制剂，用于治疗多种感染。然而，对其行动方式缺乏清晰的洞察力，目标尚未确定。克拉维酸的剂量目前基于伙伴药物（阿莫西林或替卡西林）的剂量。尽管如此，仍需要适当剂量的化合物，因为克拉维酸与副作用有关。在本系统评价中，我们旨在描述当前关于克拉维酸在儿科人群中的药代动力学的文献
方法
我们在 MEDLINE、Embase.com、Cochrane Central、Google Scholar 和 Web of Science 中进行了系统搜索。我们纳入了所有已发表的报告克拉维酸在新生儿和 0-18 岁儿童中的药代动力学数据的研究。
结果
搜索产生了 18 项符合纳入标准的原始研究。一般来说，药物暴露的变化很大，这可以部分解释为疾病状态、给药途径或年龄的差异。不幸的是，这些研究有限的背景信息阻碍了对观察到的变异性的深入评估。
结论
克拉维酸在儿科患者中的药代动力学变化很大，与成人报告相似，但更为明显。对于这种可变性的特定人群解释，仍然存在重大的知识差距。因此，需要基于模型的药代动力学研究来解决儿科人群的成熟和疾病特异性变化。此外，需要额外的药效学研究来确定明确的目标。综合结果最终将导致克拉维酸和靶向暴露的药代动力学-药效学模型。
临床试验注册
PROSPERO CRD42020137253。
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