Differences in the Pharmacokinetics of Gentamicin between Oncology and Nononcology Pediatric Patients

Llanos-Paez, Carolina; Staatz, C. E.; Lawson, Rachael; Hennig, Stefanie

doi:10.1128/aac.01730-19

Cited by 6 publications

(12 citation statements)

References 27 publications

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“…This study describes the differences in the PK of gentamicin, amikacin and vancomycin from premature neonates to adults using data from a large number of patients from different locations and different underlying medical conditions (Supporting Information Table S1). A previous study (data from sources 15 and 16 in this pooled analysis) 42 reported differences in the PK of gentamicin between oncology and non‐oncology paediatric patients by including NFM as a body size descriptor. NFM was applied 42 to describe the differences in the percentage of body fat between paediatric oncology (30.4%) and non‐oncology (14.9%).…”

Section: Discussionmentioning

confidence: 99%

A physiological approach to renal clearance: From premature neonates to adults

Holford,

O'Hanlon,

Allegaert

et al. 2024

Brit J Clinical Pharma

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AimsWe propose using glomerular filtration rate (GFR) as the physiological basis for distinguishing components of renal clearance.MethodsGentamicin, amikacin and vancomycin are thought to be predominantly excreted by the kidneys. A mixed effects joint model of the pharmacokinetics of these drugs was developed, with a wide dispersion of weight, age, and serum creatinine. A dataset created from 18 sources resulted in 27,338 drug concentrations from 9,901 patients. Body size and composition, maturation and renal function were used to describe differences in drug clearance and volume of distribution.ResultsThis study demonstrates that GFR is a predictor of two distinct components of renal elimination clearance: (1) GFR clearance associated with normal GFR and (2) non‐GFR clearance not associated with normal GFR.All three drugs had GFR clearance estimated as a drug specific percentage of normal GFR (gentamicin 39%, amikacin 90%, vancomycin 57%).The total clearance (sum of GFR and non‐GFR clearance), standardized to 70 kg total body mass, 176 cm, male, renal function 1, was 5.58 L/h (95% CI 5.50‐5.69) (gentamicin), 7.77 L/h (95 %CI 7.26‐8.19) (amikacin) and 4.70 L/h (95 %CI 4.61‐4.80) (vancomycin).ConclusionGFR provides a physiological basis for renal drug elimination. It has been used to distinguish two elimination components. This physiological approach has been applied to describe clearance and volume of distribution from premature neonates to elderly adults with a wide dispersion of size, body composition and renal function. Dose individualization has been implemented using target concentration intervention.

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Section: Discussionmentioning

confidence: 99%

A physiological approach to renal clearance: From premature neonates to adults

Holford,

O'Hanlon,

Allegaert

et al. 2024

Brit J Clinical Pharma

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“…We aimed to review the clinical pharmacokinetics and consequences for optimal dosing of gentamicin for infections caused by Gram-negative bacteria in various patient populations, focusing on new insights from the past decade. Several new PPK studies have focused on specific subpopulations including obese patients [46], critically ill patients [66,68,148], paediatric patients [90,92,106,149], neonates [112,[115][116][117][118]122], elderly patients [126] and patients on IHD [64,137], providing insights into the typical values of CL and V d in these patient groups, the variability of these parameters and possible explanations for this variability. But despite inclusion of covariates in many of these PPK models, unexplained IIV in CL and V d often remained high, especially in critically ill patients, resulting in wide ranges of C max , C min and AUC.…”

Section: Discussionmentioning

confidence: 99%

“…In infants, V d of gentamicin is estimated to be 0.35 L/kg [ 89 ], higher than reported in adults and lower compared with neonates [ 90 ]. Studies on pharmacokinetics of gentamicin in febrile neutropenic children aged 0–17 years showed a V d ranging from 0.25 L/kg to 0.32 L/kg [ 91 , 92 ].…”

Section: Pharmacokinetics In Paediatric Patientsmentioning

confidence: 99%

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Clinical Pharmacokinetics of Gentamicin in Various Patient Populations and Consequences for Optimal Dosing for Gram-Negative Infections: An Updated Review

et al. 2022

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Gentamicin is an aminoglycoside antibiotic with a small therapeutic window that is currently used primarily as part of shortterm empirical combination therapy. Gentamicin dosing schemes still need refinement, especially for subpopulations where pharmacokinetics can differ from pharmacokinetics in the general adult population: obese patients, critically ill patients, paediatric patients, neonates, elderly patients and patients on dialysis. This review summarizes the clinical pharmacokinetics of gentamicin in these patient populations and the consequences for optimal dosing of gentamicin for infections caused by Gram-negative bacteria, highlighting new insights from the last 10 years. In this period, several new population pharmacokinetic studies have focused on these subpopulations, providing insights into the typical values of the most relevant pharmacokinetic parameters, the variability of these parameters and possible explanations for this variability, although unexplained variability often remains high. Both dosing schemes and pharmacokinetic/pharmacodynamic (PK/PD) targets varied widely between these studies. A gentamicin starting dose of 7 mg/kg based on total body weight (or on adjusted body weight in obese patients) appears to be the optimal strategy for increasing the probability of target attainment (PTA) after the first administration for the most commonly used PK/PD targets in adults and children older than 1 month, including critically ill patients. However, evidence that increasing the PTA results in higher efficacy is lacking; no studies were identified that show a correlation between estimated or predicted PK/PD target attainment and clinical success. Although it is unclear if performing therapeutic drug monitoring (TDM) for optimization of the PTA is of clinical value, it is recommended in patients with highly variable pharmacokinetics, including patients from all subpopulations that are critically ill (such as elderly, children and neonates) and patients on intermittent haemodialysis. In addition, TDM for optimization of the dosing interval, targeting a trough concentration of at least < 2 mg/L but preferably < 0.5-1 mg/L, has proven to reduce nephrotoxicity and is therefore recommended in all patients receiving more than one dose of gentamicin. The usefulness of the daily area under the plasma concentration-time curve for predicting nephrotoxicity should be further investigated. Additionally, more research is needed on the optimal PK/PD targets for efficacy in the clinical situations in which gentamicin is currently used, that is, as monotherapy for urinary tract infections or as part of short-term combination therapy.

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“…Serum creatinine concentration was scaled by the expected sex‐ and age‐adjusted normal serum creatinine concentration as applied in other paediatric studies. 23 , 24 , 25 , 26 , 27 , 28 …”

Section: Methodsmentioning

confidence: 99%

Population pharmacokinetics and dose optimisation of colecalciferol in paediatric patients with chronic kidney disease

Wan

Green

Iyengar

et al. 2021

Brit J Clinical Pharma

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The prevalence of vitamin D deficiency is high in children with chronic kidney disease (CKD). However, current dosing recommendations are based on limited pharmacokinetic (PK) data. This study aimed to develop a population PK model of colecalciferol that can be used to optimise colecalciferol dosing in this population.Methods: Data from 83 children with CKD were used to develop a population PK model using a nonlinear mixed effects modelling approach. Serum creatinine and type of kidney disease (glomerular vs. nonglomerular disease) were investigated as covariates, and optimal dosing was determined based on achieving and maintaining 25-hydroxyvitamin D (25(OH)D) concentration of 30-48 ng/mL. Results:The time course of 25(OH)D concentrations was best described by a 1-compartment model with the addition of a basal concentration parameter to reflect endogenous 25(OH)D production from diet and sun exposure. Colecalciferol showed wide between-subject variability in its PK, with total body weight scaled allometrically the only covariate included in the model. Model-based simulations showed that current dosing recommendations for colecalciferol can be optimised using a weightbased dosing strategy.

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Differences in the Pharmacokinetics of Gentamicin between Oncology and Nononcology Pediatric Patients

Cited by 6 publications

References 27 publications

A physiological approach to renal clearance: From premature neonates to adults

A physiological approach to renal clearance: From premature neonates to adults

Clinical Pharmacokinetics of Gentamicin in Various Patient Populations and Consequences for Optimal Dosing for Gram-Negative Infections: An Updated Review

Population pharmacokinetics and dose optimisation of colecalciferol in paediatric patients with chronic kidney disease

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