Creatinine‐Based Renal Function Assessment in Pediatric Drug Development: An Analysis Using Clinical Data for Renally Eliminated Drugs

Zhang, Yifei; Sherwin, Catherine M.T.; González, Daniel; Zhang, Qunshu; Khurana, Mona; Fisher, J. Edward; Burckart, Gilbert J.; Wang, Yaning; Yao, Lynne; Ganley, Charles J.; Wang, Jian

doi:10.1002/cpt.1991

Cited by 11 publications

(18 citation statements)

References 22 publications

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“…These covariate relationships can include empirical bodyweight-based equations and/or other equations based on size, age, or disease-related descriptors. This approach is based on similar principles as those applied when using a maturation function for GFR to establish dose adjustments for GFR cleared drugs [39,40].…”

Section: Between-drug Extrapolation Of Pathway-specific Pediatric Cov...mentioning

confidence: 99%

An Update on the Use of Allometric and Other Scaling Methods to Scale Drug Clearance in Children: Towards Decision Tables

Rongen

Krekels

Calvier

et al. 2022

Expert Opinion on Drug Metabolism & Toxicology

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Introduction: When pediatric data are not available for a drug, allometric and other methods are applied to scale drug clearance across the pediatric age-range from adult values. This is applied when designing first-in-child studies, but also for off-label drug prescription. Areas covered: This review provides an overview of the systematic accuracy of allometric and other pediatric clearance scaling methods compared to gold-standard PBPK predictions. The findings are summarized in decision tables to provide a priori guidance on the selection of appropriate pediatric clearance scaling methods for both novel drugs for which no pediatric data are available and existing drugs in clinical practice. Expert opinion: While allometric scaling principles are commonly used to scale pediatric clearance, there is no universal allometric exponent (i.e. 1, 0.75, or 0.67) that can accurately scale clearance for all drugs from adults to children of all ages. Therefore, pediatric scaling decision tables based on age, drug elimination route, binding plasma protein, fraction unbound, extraction ratio, and/or isoenzyme maturation are proposed to a priori select the appropriate (allometric) clearance scaling method, thereby reducing the need for full PBPK-based clearance predictions. Guidance on allometric scaling when estimating pediatric clearance values is provided as well.

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Section: Between-drug Extrapolation Of Pathway-specific Pediatric Cov...mentioning

confidence: 99%

An Update on the Use of Allometric and Other Scaling Methods to Scale Drug Clearance in Children: Towards Decision Tables

Rongen

Krekels

Calvier

et al. 2022

Expert Opinion on Drug Metabolism & Toxicology

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“…The eGFR levels were elevated slowly from the start of amikacin therapy, consistent with former research, which were the clinical manifestations of nephrotoxicity. 20 21 Apart from renal damage induced by diseases, the kidney function of the elderly and infants were also weaker than in healthy people. Among healthy adults, there was an obvious linear decline of eGFR at about 0.75 mL/min per year, and by the age of 90 years the average of eGFR was found to be reduced by 46% compared with younger adults.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic drug monitoring of amikacin: quantification in plasma by liquid chromatography-tandem mass spectrometry and work experience of clinical pharmacists

Cheng

Zhu

et al. 2021

Eur J Hosp Pharm

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Objectives As part of the service provided by clinical pharmacists in our hospital, an assay for plasma amikacin quantification by liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been established for clinical use since 2018. This study was undertaken to describe: (1) the establishment of this assay; (2) the application and results of the testing; and (3) the analysis and impact for patients. Methods The amikacin quantification assay was validated and the plasma amikacin concentration data were extracted and analysed. The clinical data for related patients were collected from electronic health and medical records. Results 121 plasma samples from 53 patients were included in this statistical analysis. The use of amikacin was mostly monitored in the intensive care unit and the haematology department, and the monitoring range of amikacin concentrations were about 0.1–57µg/mL. The main indications for amikacin concentration detection were combined medications, impaired renal function, or people over 65 years old, which may increase the incidence of adverse reactions. Amikacin prescribing decisions were diversified due to the combination of assay results and clinical disease progression, and the effective rate of amikacin administration was about 52.8% (28/53). Conclusions The assay for plasma amikacin concentration has been successfully established to monitor the clinical use of amikacin, and the assay results served as one of the references for amikacin prescribing decisions.

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“…Similarity was a priori considered as individual eGFR values that differed <30% from mGFR values 32 , 33 . To enable comparison of our k-value with existing k-values used in neonates by Schwartz et al (k=0.45) 3 and Zhang et al (k=0.277), 4 we included these values in our analysis.…”

Section: Methodsmentioning

confidence: 99%

Maturation of GFR in Term-Born Neonates: An Individual Participant Data Meta-Analysis

Smeets

IntHout

Burgh

et al. 2022

JASN

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Background: The evidence from individual studies to support the maturational pattern of glomerular filtration rate (GFR) in healthy term-born neonates is inconclusive. We performed an individual participant data (IPD) meta-analysis of reported measured GFR (mGFR) data aimed to establish neonatal GFR reference values. Furthermore, we aimed to optimise neonatal creatinine-based GFR estimations Methods: We identified studies reporting mGFR measured by exogenous markers or creatinine clearance (CrCL) in healthy term-born neonates. The relationship between postnatal age and clearance was investigated using cubic splines with generalized additive linear mixed models. From our reference values, we estimated an updated coefficient for the Schwartz equation (eGFR(ml/min/1.73m2)=(k*height (cm))/serum creatinine(mg/dl)). Results: Forty-eight out of 1521 screened articles reported mGFR in healthy term-born neonates, and 978 mGFR values from 881 neonates were analysed. IPD were available for 367 neonates and the other 514 neonates were represented by 41 aggregated data points as means/medians per group. GFR doubled in the first five days after birth from 19.6 (95%CI 14.7;24.6) ml/min/1.73m2 to 40.6 (95%CI 36.7;44.5) ml/min/1.73m2, then more gradually increased to 59.4 (95%CI 45.9;72.9) ml/min/1.73m2 by four weeks of age. A coefficient of 0.31 to estimate GFR best fitted the data. Conclusions: These reference values for healthy term-born neonates show a biphasic increase in GFR with the largest increase between days 1 and 5. Together with the re-examined Schwartz equation, this can help identify altered GFR in term-born neonates. To enable widespread implementation of our proposed eGFR equation, validation in a large cohort of neonates is required.

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Creatinine‐Based Renal Function Assessment in Pediatric Drug Development: An Analysis Using Clinical Data for Renally Eliminated Drugs

Cited by 11 publications

References 22 publications

An Update on the Use of Allometric and Other Scaling Methods to Scale Drug Clearance in Children: Towards Decision Tables

An Update on the Use of Allometric and Other Scaling Methods to Scale Drug Clearance in Children: Towards Decision Tables

Therapeutic drug monitoring of amikacin: quantification in plasma by liquid chromatography-tandem mass spectrometry and work experience of clinical pharmacists

Maturation of GFR in Term-Born Neonates: An Individual Participant Data Meta-Analysis

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