Department of Pediatrics, Division of Neonatology, Erasmus MC Sophia Children's Hospital, Erasmus University Medical Center Rotterdam, Doctor Molenwaterplein 40, 3015 CN, Rotterdam, The Netherlands.
Department of Pediatrics, Franciscus Gasthuis and Vlietland, Rotterdam, The Netherlands.
Clin Pharmacokinet. 2022 May;61(5):637-653. doi: 10.1007/s40262-022-01116-3. Epub 2022 Mar 31.
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.
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.
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.
PROSPERO CRD42020137253.
克拉维酸是儿科常用的β-内酰胺酶抑制剂，可用于多种感染。然而，其作用机制尚不清楚，也尚未确定其作用靶点。克拉维酸的剂量目前基于其配伍药物（阿莫西林或替卡西林）。尽管如此，仍需要正确给药，因为克拉维酸与不良反应有关。在本系统评价中，我们旨在描述儿科人群中克拉维酸的药代动力学的现有文献。
我们在 MEDLINE、Embase.com、Cochrane Central、Google Scholar 和 Web of Science 中进行了系统搜索。我们纳入了所有报告新生儿和 0-18 岁儿童克拉维酸药代动力学数据的已发表研究。
搜索结果包括 18 项符合纳入标准的原始研究。一般来说，药物暴露的变异性很大，这部分可以用疾病状态、给药途径或年龄的差异来解释。不幸的是，研究中有限的背景信息妨碍了对观察到的变异性的深入评估。
儿科患者克拉维酸的药代动力学高度可变，与成人报告相似，但更明显。关于这种变异性的人群特异性解释仍存在显著的知识空白。因此，需要针对儿科人群进行基于模型的药代动力学研究，以解决成熟和疾病特异性变化。此外，还需要额外的药效学研究来确定明确的目标。综合结果将最终导致克拉维酸的药代动力学-药效学建模和靶向暴露。
PROSPERO CRD42020137253。
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