Determinants of gentamicin concentrations in critically ill patients: a population pharmacokinetic analysis

Hodiamont, Caspar J.; Juffermans, Nicole P.; Bouman, Catherine S. C.; Jong, Menno D. de; Mathôt, Ron A. A.; Hest, Reinier M. van

doi:10.1016/j.ijantimicag.2016.10.022

Cited by 31 publications

(73 citation statements)

References 36 publications

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“…A one-compartment model adequately described gentamicin PK, and comparable to what can be found in septic ICU patients, the estimated V and CL in this study's non-ICU population were high, as were the BPVs of these PK parameters (19,20). Once-daily gentamicin dosing with the commonly recommended initial regimen for non-ICU patients in the SSA setting is likely to lead to insufficient peak concentrations.…”

supporting

confidence: 65%

Population Pharmacokinetics with Monte Carlo Simulations of Gentamicin in a Population of Severely Ill Adult Patients from Sub-Saharan Africa

Bos

Prins

Mistício

et al. 2019

Antimicrob Agents Chemother

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In sub-Saharan Africa (SSA), gentamicin is commonly used for severe infections in non-intensive-care-unit (ICU) settings, but pharmacokinetic and pharmacodynamic data for this specific population are lacking. We performed a population pharmacokinetic study in an adult Mozambican non-ICU hospital population treated with gentamicin (n ϭ 48) and developed a pharmacokinetic model using nonlinear mixed-effects modeling. Simulations showed that non-ICU patient populations in SSA may be at substantial risk for underexposure to gentamicin during routine once-daily dosing.

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supporting

confidence: 65%

Population Pharmacokinetics with Monte Carlo Simulations of Gentamicin in a Population of Severely Ill Adult Patients from Sub-Saharan Africa

Bos

Prins

Mistício

et al. 2019

Antimicrob Agents Chemother

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“…Allou et al suggested a gentamicin dose of 11 mg/kg of IBW to achieve the therapeutic target [38]. Hodiamont et al performed population-based PK analysis for gentamicin and used IBW to describe its distribution volume and clearance [39]. One may be surprised by the influence of renal function on the achievement of amikacin target peak identified in this study, considering that this covariate is expected to mostly influence amikacin clearance but not its volume of distribution.…”

Section: Discussionmentioning

confidence: 76%

“…Allou et al suggested a gentamicin dose of 11 mg/kg of IBW to achieve the therapeutic target . Hodiamont et al performed population‐based PK analysis for gentamicin and used IBW to describe its distribution volume and clearance .…”

Section: Discussionmentioning

confidence: 99%

Determinants of amikacin first peak concentration in critically ill patients

Boidin

Jenck

Bourguignon

et al. 2018

Fundamemntal Clinical Pharma

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Amikacin antimicrobial effect has been correlated with the ratio of the peak concentration (C ) to the minimum inhibitory concentration. A target C ≥ 60-80 mg/L has been suggested. It has been shown that such target is not achieved in a large proportion of critically ill patients in intensive care units. A retrospective analysis was performed to examine the determinants of C ≥ 80 mg/L on the first peak in 339 critically ill patients treated by amikacin. The influence of available variables on C target attainment was analyzed using a classification and regression tree (CART) and logistic regression. Mean C in the 339 patients was 73.0 ± 23.9 mg/L, with a target attainment rate (TAR, C ≥ 80 mg/L) of 37.5%. In CART analysis, the strongest predictor of amikacin target peak attainment was dose per kilogram of lean body weight (dose/LBW). TAR was 60.1% in patients with dose/LBW ≥ 37.8 vs. 19.9% in patients with lower dose/LBW (OR = 6.0 (95% CI: 3.6-10.2)). Renal function was a secondary predictor of C . Logistic regression analysis identified dose per kilogram of ideal body weight (OR = 1.13 (95% CI: 1.09-1.17)) and creatinine clearance (OR = 0.993 (95% CI: 0.988-0.998)) as predictors of target peak achievement. Based on our results, an amikacin dose ≥ 37.8 mg/kg of LBW should be used to optimize the attainment of C ≥ 80 mg/L after the first dose in critically ill patients. An even higher dose may be necessary in patients with normal renal function.

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“…Previously, Hodiamont et al developed a population PK model for gentamicin in ICU patients. [12] Plasma albumin concentrations were identified as a significant covariate on the central volume of distribution. Continuous venovenous hemofiltration (CVVH) and creatinine clearance calculated based on a 6 hour urine portion (CalcCL cr ), as a measure of renal function were identified as covariates on clearance.…”

Section: Introductionmentioning

confidence: 99%

“…Continuous venovenous hemofiltration (CVVH) and creatinine clearance calculated based on a 6 hour urine portion (CalcCL cr ), as a measure of renal function were identified as covariates on clearance. [12] External validation of this model is necessary to confirm whether this model can reliably be used for calculation of the appropriate gentamicin (starting) doses. The aim of this study was to externally validate the ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T 6 previously developed population PK model by evaluating its predictive performance in cohorts from two different ICUs.…”

Section: Introductionmentioning

confidence: 99%

Predictive performance of a gentamicin population pharmacokinetic model in two western populations of critically ill patients

Bukkems

Roger

Hodiamont

et al. 2018

International Journal of Antimicrobial Agents

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Determinants of gentamicin concentrations in critically ill patients: a population pharmacokinetic analysis

Cited by 31 publications

References 36 publications

Population Pharmacokinetics with Monte Carlo Simulations of Gentamicin in a Population of Severely Ill Adult Patients from Sub-Saharan Africa

Population Pharmacokinetics with Monte Carlo Simulations of Gentamicin in a Population of Severely Ill Adult Patients from Sub-Saharan Africa

Determinants of amikacin first peak concentration in critically ill patients

Predictive performance of a gentamicin population pharmacokinetic model in two western populations of critically ill patients

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