Extended-interval gentamicin: Population pharmacokinetics in pediatric critical illness

TY - JOUR

T1 - Extended-interval gentamicin

T2 - Population pharmacokinetics in pediatric critical illness

AU - Lopez, Sara Arenas

AU - Mulla, Hussain

AU - Durward , Andrew

AU - Tibby, Shane

PY - 2010/3

Y1 - 2010/3

N2 - 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. 

AB - 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. 

KW - gentamicin

KW - aminoglycoside

KW - pharmacokinetics

KW - critical illness

KW - intensive care

KW - child

KW - neonate

KW - BLOOD-STREAM INFECTION

KW - AMINOGLYCOSIDE THERAPY

KW - QUANTIFICATION LIMIT

KW - ADULT PATIENTS

KW - ILL ADULT

KW - CHILDREN

KW - METAANALYSIS

KW - INFANTS

KW - SINGLE

KW - IMPACT

U2 - 10.1097/PCC.0b013e3181b80693

DO - 10.1097/PCC.0b013e3181b80693

M3 - Article

SN - 1529-7535

VL - 11

SP - 267

EP - 274

JO - Pediatric Critical Care Medicine

JF - Pediatric Critical Care Medicine

IS - 2

ER -