Pharmacokinetics of Clavulanic Acid in the Pediatric Population: A Systematic Literature Review

Abstract

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. Supplementary Information The online version contains supplementary material available at 10.1007/s40262-022-01116-3.

A systematic review of the effect of renal replacement therapy on the pharmacokinetics of co-amoxiclav

“…Data from a study assessing the stability of amoxicillin and clavulanic acid showed that amoxicillin retained 90% of its initial concentration for 80.3 h at 4°C, 24.8h at 25°C and 9h at 37°C; clavulanic acid retained 90% of its initial concentration for 152 h at 4°C, 26h at 25°C and 6.4h at 37°C [20]. Studies have recommended storing clavulanic acid at -80°C within 1 h after withdrawal due to the poor stability of clavulanic acid [21]. None of the studies reported the time period between sampling and refrigeration, or the storage period.…”

Developmental Pharmacokinetics of Antibiotics Used in Neonatal ICU: Focus on Preterm Infants

“…Amoxicillin clavulanate is one of the most prescribed oral antibiotics for both adult and pediatric populations used in case of proved or strictly suspected beta-lactamase production. Evaluation of PK parameters of oral clavulanic acid in term neonates ( n —15, dose of amoxicillin clavulanate 25/6.25 mg/kg, thrice a day administration) resulted in great variance in plasma concentrations (median: 1.4 mg/L; range: 0.20–4.82 mg/L) and extrapolation led to AUC of at least 8.4 mg·h/L, which is comparable to those of adults [ 73 ]. The conclusion of high variability of PK parameters of clavulanic acid in the pediatric population is supported by a systemic literature review of 18 studies, which did also state that C max , for oral administration, was below that of the intravenous route [ 73 ], which is like it is in adults [ 74 ].…”

Quality of Amoxicillin Trihydrate/Potassium Clavulanate Tablets Commercially Available in Libyan Pharmaceutical Market

“…273.3], (fig. 2) belongs to β-lactam inhibitors, which acts by preventing bacteria from destroying the action of AC and enhancing the spectrum range of AC [16,17].…”