Extended-interval gentamicin: Population pharmacokinetics in pediatric critical illness

Sara Arenas Lopez*, Hussain Mulla, Andrew Durward , Shane Tibby

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    40 Citations (Scopus)

    Abstract

    Objectives: Once-daily gentamicin therapy is becoming increasingly common in pediatric practice; however, little is known about pharmacokinetics in critical illness. Gentamicin exhibits concentration dependant killing; thus, peak serum concentrations at least eight times higher than minimum inhibition concentration of the target organism have been recommended. We wanted to derive pharmacokinetic parameters for gentamicin in critical illness and to evaluate whether a dose of 8 mg/kg provides an adequate peak serum concentration (>16 mg/L).

    Patients and Interventions: Population-based pharmacokinetic analyses were undertaken using therapeutic drug monitoring data collected prospectively in an intensive care unit over 6 months (n = 50 children). Monte Carlo simulations were used to estimate the probability of achieving 1) peak concentrations >16 mg/L; and 2) trough concentrations <2 mg/L at 24 and 36 hrs.

    Measurements and Main Results: The optimal pharmacokinetic model was of two-compartment disposition with zero order input and additive residual error. Weight was associated nonlinearly with clearance and linearly with volume, and age was a significant covariate for clearance. An 8-mg/kg dose provided near 100% probability of achieving adequate peak concentrations at all ages. However this probability decreased rapidly at doses 24 hrs.

    Conclusions: A gentamicin dose of 8 mg/kg is highly likely to achieve peak concentrations >16 mg/L in critically ill children. A considerable proportion will require dose intervals >24 hrs; thus, therapeutic drug monitoring is essential. 

    Original languageEnglish
    Pages (from-to)267-274
    Number of pages8
    JournalPediatric Critical Care Medicine
    Volume11
    Issue number2
    DOIs
    Publication statusPublished - Mar 2010

    Keywords

    • gentamicin
    • aminoglycoside
    • pharmacokinetics
    • critical illness
    • intensive care
    • child
    • neonate
    • BLOOD-STREAM INFECTION
    • AMINOGLYCOSIDE THERAPY
    • QUANTIFICATION LIMIT
    • ADULT PATIENTS
    • ILL ADULT
    • CHILDREN
    • METAANALYSIS
    • INFANTS
    • SINGLE
    • IMPACT

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