Maturation of the Glomerular Filtration Rate in Neonates, as Reflected by Amikacin Clearance

Cock, Roosmarijn F. W. De; Allegaert, Karel; Schreuder, Michiel F.; Sherwin, Catherine M.T.; Hoog, Matthijs de; Anker, Johannes N. van den; Danhof, Meindert; Knibbe, Catherijne A. J.

doi:10.2165/11595640-000000000-00000

Cited by 102 publications

(168 citation statements)

References 40 publications

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“…While pediatric dosing regimens are mostly empirically derived using extrapolations based on body weight (2,3), it has been shown before that dosing in children should be guided by the understanding of developmental changes in the pharmacokinetic and/or pharmacodynamic relation of drugs (2,4,5). More specifically, translation of results from pharmacokinetic modeling studies has been shown to result in individualized dosing guidelines for many different drugs in pediatric clinical practice (5)(6)(7)(8)(9).…”

mentioning

confidence: 99%

Towards Rational Dosing Algorithms for Vancomycin in Neonates and Infants Based on Population Pharmacokinetic Modeling

Janssen

Välitalo

Allegaert

et al. 2016

Antimicrob Agents Chemother

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iBecause of the recent awareness that vancomycin doses should aim to meet a target area under the concentration-time curve (AUC) instead of trough concentrations, more aggressive dosing regimens are warranted also in the pediatric population. In this study, both neonatal and pediatric pharmacokinetic models for vancomycin were externally evaluated and subsequently used to derive model-based dosing algorithms for neonates, infants, and children. For the external validation, predictions from previously published pharmacokinetic models were compared to new data. Simulations were performed in order to evaluate current dosing regimens and to propose a model-based dosing algorithm. The AUC/MIC over 24 h (AUC 24 /MIC) was evaluated for all investigated dosing schedules (target of >400), without any concentration exceeding 40 mg/liter. Both the neonatal and pediatric models of vancomycin performed well in the external data sets, resulting in concentrations that were predicted correctly and without bias. For neonates, a dosing algorithm based on body weight at birth and postnatal age is proposed, with daily doses divided over three to four doses. For infants aged <1 year, doses between 32 and 60 mg/kg/day over four doses are proposed, while above 1 year of age, 60 mg/kg/day seems appropriate. As the time to reach steady-state concentrations varies from 155 h in preterm infants to 36 h in children aged >1 year, an initial loading dose is proposed. Based on the externally validated neonatal and pediatric vancomycin models, novel dosing algorithms are proposed for neonates and children aged <1 year. For children aged 1 year and older, the currently advised maintenance dose of 60 mg/kg/day seems appropriate. In the pediatric population, drugs are often administered in an off-label or unlicensed manner (1). While pediatric dosing regimens are mostly empirically derived using extrapolations based on body weight (2, 3), it has been shown before that dosing in children should be guided by the understanding of developmental changes in the pharmacokinetic and/or pharmacodynamic relation of drugs (2, 4, 5). More specifically, translation of results from pharmacokinetic modeling studies has been shown to result in individualized dosing guidelines for many different drugs in pediatric clinical practice (5-9).The antibacterial agent vancomycin is commonly used to treat infections caused by Gram-positive organisms, like methicillinresistant Staphylococcus aureus (MRSA) and amoxicillin-resistant Enterococcus species, in both adults and pediatric patients (10). In neonates, MRSA infection is relatively rare, and coagulase-negative staphylococci are the most commonly identified infectious organisms necessitating vancomycin treatment (11,12). For vancomycin, it has been shown that bacterial killing of S. aureus is best predicted by the area under the concentration-time curve over 24 h (AUC 24 ) divided by the MIC for the infecting pathogen (AUC 24 / MIC) (13-15). In adult patients, an AUC 24 /MIC of Ն400 resulted in a superior clinical and...

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mentioning

confidence: 99%

Towards Rational Dosing Algorithms for Vancomycin in Neonates and Infants Based on Population Pharmacokinetic Modeling

Janssen

Välitalo

Allegaert

et al. 2016

Antimicrob Agents Chemother

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“…As mentioned, the limitation of this study was that the majority of patients were neonatal age 1 -2 days, while other age categories (up to 1 month) included only 1 -2 patients. Consequently, it was not possible to observe the tendency of the changes in CL and t 1/2 during the neonatal period in the present study, but it has been shown by population pharmacokinetic models (18). However, based on the presented results it may be reasonable to explain the variability in CL with neonatal age and kidney maturation.…”

Section: Discussionmentioning

confidence: 53%

“…Additionally, the developed predictive pharmacokinetic-pharmacodynamic model for gentamicin dosing schedules in neonates supported equivalent efficacy when the dosing interval was 24, 36, or 48 h for the same total dose (28). This result may be extrapolated to amikacin as well, where C trough after OD can be targeted at 1.5 to 3 mg/ml (18,29). In our study, 53.33% of patients in the OD group had C trough > 3 mg/ml.…”

Section: Discussionmentioning

confidence: 84%

“…The findings of other authors confirm that variability in amikacin elimination was caused by gestation age or birth weight which correlates to gestation age. However, in these studies, pre-and full-term neonates were included (10,18,30). There were as well conflicting data if postmenstrual (sum of gestational and neonatal) age was a good predictor of aminoglycoside CL (12,17,23,31).…”

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetic Variability of Amikacin After Once-Daily and Twice-Daily Dosing Regimen in Full-Term Neonates

Vučićević¹,

Rakonjac

Miljković³

et al. 2014

J Pharmacol Sci

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Abstract. The purpose of the study was to compare peak (C peak ) and trough (C trough ) amikacin levels after twice-daily (TD) or once-daily dosing (OD) in full-term neonates. Additionally, the study aimed to address amikacin pharmacokinetics and its variability. Data included 31 patients born on term. Amikacin daily dose was 15 or 20 mg/kg depending on the neonate's age. Patients randomly received amikacin every 12 or 24 h. In all patients corresponding C peak and C trough were taken. Volume of distribution (Vd), clearance (CL) and half-life (t 1/2 ) were calculated. Mean C peak of 21.79 mg/ml in the TD group was statistically different from C peak of 36.39 mg/ml in the OD group. Average C trough in TD (5.67 mg/ml) was statistically different from the corresponding 3.99 mg/ml in the OD group. Mean amikacin Vd, CL, and t 1/2 were 0.78 ± 0.38 l/kg, 86.99 ± 48.22 ml/h•kg, and 6.81 ± 2.51 h, respectively. High interindividual pharmacokinetic variability was observed. Further analysis showed that neonatal age contributed to the pharmacokinetic parameters' values. Statistically significant difference in CL and t 1/2 was observed between patients age ≤ 2 and > 2 days on therapy initiation. As expected, amikacin given OD achieved higher C peak and lower C trough than TD. Based on the results, observed variability in amikacin pharmacokinetics was possibly due to the renal maturation process.

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“…Pediatric developmental changes must be taken into account, as they also play a key role in pharmacokinetics. For example, obvious maturation changes are related to the volume increase of luminal fluids, intestinal surface area, and intestinal permeability (12)(13)(14)(15). Administered dose is also fundamentally important, and therefore, there may be a need for a more quantitative, dose-dependent approach to pediatric BCS (16,17).…”

Section: Challenges In the Development Of Pediatric Dosage Forms Frommentioning

confidence: 99%

A Report from the Pediatric Formulations Task Force: Perspectives on the State of Child-Friendly Oral Dosage Forms

Zajicek

Fossler

Barrett

et al. 2013

AAPS J

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Abstract. Despite the fact that a significant percentage of the population is unable to swallow tablets and capsules, these dosage forms continue to be the default standard. These oral formulations fail many patients, especially children, because of large tablet or capsule size, poor palatability, and lack of correct dosage strength. The clinical result is often lack of adherence and therapeutic failure. The American Association of Pharmaceutical Scientists formed a Pediatric Formulations Task Force, consisting of members with various areas of expertise including pediatrics, formulation development, clinical pharmacology, and regulatory science, in order to identify pediatric, manufacturing, and regulatory issues and areas of needed research and regulatory guidance. Dosage form and palatability standards for all pediatric ages, relative bioavailability requirements, and small batch manufacturing capabilities and creation of a viable economic model were identified as particular needs. This assessment is considered an important first step for a task force seeking creative approaches to providing more appropriate oral formulations for children.

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Maturation of the Glomerular Filtration Rate in Neonates, as Reflected by Amikacin Clearance

Cited by 102 publications

References 40 publications

Towards Rational Dosing Algorithms for Vancomycin in Neonates and Infants Based on Population Pharmacokinetic Modeling

Towards Rational Dosing Algorithms for Vancomycin in Neonates and Infants Based on Population Pharmacokinetic Modeling

Pharmacokinetic Variability of Amikacin After Once-Daily and Twice-Daily Dosing Regimen in Full-Term Neonates

A Report from the Pediatric Formulations Task Force: Perspectives on the State of Child-Friendly Oral Dosage Forms

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