We aimed to quantify amikacin pharmacokinetics (PK) and early target attainment using routine third-dose therapeutic drug monitoring (TDM) in pediatric intensive care unit (PICU) patients and to identify clinical covariates associated with volume of distribution (Vd) and clearance (CL). We conducted a retrospective cohort study of PICU patients who received intravenous amikacin between January 2022 and December 2023. Individual PK parameters were estimated using third-dose peak and trough concentrations via the Sawchuk-Zaske method. Clinical and laboratory covariates were evaluated for associations with Vd and CL. Among 210 patients, mean Vd was 0.59 ± 0.30 L/kg and mean CL was 0.08 ± 0.03 L/kg/h. Early target under attainment was frequent, with 23.3% of <InlineEquation ID="IEq1"> <EquationSource Format="TEX">${C}_{\text{max}}$</EquationSource> <EquationSource Format="MATHML"><math> <msub> <mi>C</mi> <mtext>max</mtext> </msub> </math></EquationSource> </InlineEquation> and 7.6% of <InlineEquation ID="IEq2"> <EquationSource Format="TEX">${C}_{\text{min}}$</EquationSource> <EquationSource Format="MATHML"><math> <msub> <mi>C</mi> <mtext>min</mtext> </msub> </math></EquationSource> </InlineEquation> values outside therapeutic targets. Independent predictors of Vd included age, creatinine clearance (CrCl), and alanine aminotransferase (ALT), while CL was independently associated with age, CrCl, urea, and ALT. Conclusion: Critically ill children demonstrate expanded Vd and increased CL, contributing to inadequate early amikacin exposure under standard dosing. Early PK-guided dosing and model-informed strategies may improve target attainment and individualized therapy in this high-risk population. What is Known: Amikacin PK in children is variable, and standard dosing may not consistently achieve therapeutic targets. Critically ill pediatric patients often experience altered drug disposition and clearance, which can affect amikacin exposure and response. What is New: This study quantified amikacin PK parameters in critically ill children receiving routine TDM in the PICU. Expanded Vd and increased CL were identified, with age, CrCl, urea, and ALT associated with variability in amikacin PK.

Amikacin pharmacokinetics, target attainment, and predictors in critically ill children: a retrospective cohort

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2026年4月13日

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Chin Chiang Toh,
Jian Lynn Lee,
Mohd Makmor Bakry,
Noraida Mohamed Shah,
Shamin Mohd Saffian

摘要

We aimed to quantify amikacin pharmacokinetics (PK) and early target attainment using routine third-dose therapeutic drug monitoring (TDM) in pediatric intensive care unit (PICU) patients and to identify clinical covariates associated with volume of distribution (Vd) and clearance (CL). We conducted a retrospective cohort study of PICU patients who received intravenous amikacin between January 2022 and December 2023. Individual PK parameters were estimated using third-dose peak and trough concentrations via the Sawchuk-Zaske method. Clinical and laboratory covariates were evaluated for associations with Vd and CL. Among 210 patients, mean Vd was 0.59 ± 0.30 L/kg and mean CL was 0.08 ± 0.03 L/kg/h. Early target under attainment was frequent, with 23.3% of ${C}_{\text{max}}$ $C_{max}$ and 7.6% of ${C}_{\text{min}}$ $C_{min}$ values outside therapeutic targets. Independent predictors of Vd included age, creatinine clearance (CrCl), and alanine aminotransferase (ALT), while CL was independently associated with age, CrCl, urea, and ALT. Conclusion: Critically ill children demonstrate expanded Vd and increased CL, contributing to inadequate early amikacin exposure under standard dosing. Early PK-guided dosing and model-informed strategies may improve target attainment and individualized therapy in this high-risk population. What is Known: Amikacin PK in children is variable, and standard dosing may not consistently achieve therapeutic targets. Critically ill pediatric patients often experience altered drug disposition and clearance, which can affect amikacin exposure and response. What is New: This study quantified amikacin PK parameters in critically ill children receiving routine TDM in the PICU. Expanded Vd and increased CL were identified, with age, CrCl, urea, and ALT associated with variability in amikacin PK.