Amikacin nomogram for treatment of adult cystic fibrosis exacerbations based on an external evaluation of a population pharmacokinetic model

2020 ◽  
Vol 55 (5) ◽  
pp. 1154-1160 ◽  
Author(s):  
Daniel J. G. Thirion ◽  
Valérian Pasche ◽  
Elias Matouk ◽  
Amélie Marsot
Keyword(s):  
Cystic Fibrosis ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Population Pharmacokinetic ◽  
External Evaluation

Reply to Baklouti et al., “Why Is It Desirable To Do the External Evaluation of a Population Pharmacokinetic Model?”

2021 ◽  
Author(s):  
Pier Giorgio Cojutti ◽  
Matteo Rinaldi ◽  
Eleonora Zamparini ◽  
Nicolò Rossi ◽  
Sara Tedeschi ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Optimal Treatment ◽  
Adult Patients ◽  
Population Pharmacokinetic ◽  
External Evaluation ◽  
Population Pharmacokinetic Study ◽  
Osteoarticular Infections ◽  
French Group

We thank Baklouti et al. (1) for commenting on our population pharmacokinetic study of dalbavancin for optimal treatment of adult patients with staphylococcal osteoarticular infections (2) and for suggesting that our model tends to underestimate the concentrations observed in a group of French patients (French group).…

scholarly journals External Evaluation of a Gentamicin Infant Population Pharmacokinetic Model Using Data from a National Electronic Health Record Database

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Shufan Ge ◽  
Ryan J. Beechinor ◽  
Christoph P. Hornik ◽  
Joseph F. Standing ◽  
Kanecia Zimmerman ◽  
...  
Keyword(s):  
Electronic Health Record ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Population Pharmacokinetic ◽  
Health Record ◽  
External Evaluation ◽  
Data Source ◽  
Electronic Health ◽  
Using Data ◽  
Neonates And Infants

ABSTRACTGentamicin is a common antibiotic used in neonates and infants. A recently published population pharmacokinetic (PK) model was developed using data from multiple studies, and the objective of our analyses was to evaluate the feasibility of using a national electronic health record (EHR) database for further external evaluation of this model. Our results suggest that, with proper data capture procedures, EHR data can serve as a potential data source for external evaluation of PK models.

scholarly journals A Population Pharmacokinetic Model of Gentamicin in Pediatric Oncology Patients To Facilitate Personalized Dosing

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
C. C. Llanos-Paez ◽  
C. E. Staatz ◽  
R. Lawson ◽  
S. Hennig
Keyword(s):  
Pediatric Oncology ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Volume Of Distribution ◽  
Population Pharmacokinetic ◽  
Parameter Estimates ◽  
External Evaluation ◽  
Oncology Patients ◽  
Mixed Effect ◽  
Final Model

ABSTRACT To ensure the safe and effective dosing of gentamicin in children, therapeutic drug monitoring (TDM) is recommended. TDM utilizing Bayesian forecasting software is recommended but is unavailable, as no population model that describes the pharmacokinetics of gentamicin in pediatric oncology patients exists. This study aimed to develop and externally evaluate a population pharmacokinetic model of gentamicin to support personalized dosing in pediatric oncology patients. A nonlinear mixed-effect population pharmacokinetic model was developed from retrospective data. Data were collected from 423 patients for model building and a further 52 patients for external evaluation. A two-compartment model with first-order elimination best described the gentamicin disposition. The final model included renal function (described by fat-free mass and postmenstrual age) and the serum creatinine concentration as covariates influencing gentamicin clearance (CL). Final parameter estimates were as follow CL, 5.77 liters/h/70 kg; central volume of distribution, 21.6 liters/70 kg; peripheral volume of distribution, 13.8 liters/70 kg; and intercompartmental clearance, 0.62 liter/h/70 kg. External evaluation suggested that current models developed in other pediatric cohorts may not be suitable for use in pediatric oncology patients, as they showed a tendency to overpredict the observations in this population. The final model developed in this study displayed good predictive performance during external evaluation (root mean square error, 46.0%; mean relative prediction error, −3.40%) and may therefore be useful for the personalization of gentamicin dosing in this cohort. Further investigations should focus on evaluating the clinical application of this model.

scholarly journals Population Pharmacokinetic Model for Intravenous ASN100 in Healthy Subjects

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S529-S529
Author(s):  
Scott A Van Wart ◽  
Christopher Stevens ◽  
Zoltan Magyarics ◽  
Steven A Luperchio ◽  
Paul G Ambrose
Keyword(s):  
Healthy Subjects ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Population Pharmacokinetic

scholarly journals Pharmacokinetics and Pharmacogenetics of Cyclophosphamide in a Neonate and Infant Childhood Cancer Patient Population

2021 ◽  
Vol 14 (3) ◽  
pp. 272
Author(s):  
Shelby Barnett ◽  
Julie Errington ◽  
Julieann Sludden ◽  
David Jamieson ◽  
Vianney Poinsignon ◽  
...  
Keyword(s):  
Cancer Patient ◽  
Childhood Cancer ◽  
Patient Population ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Drug Clearance ◽  
Current Data ◽  
Population Pharmacokinetic ◽  
Older Children ◽  
Patient Groups

Infants and young children represent an important but much understudied childhood cancer patient population. The pharmacokinetics and pharmacogenetics of the widely used anticancer prodrug cyclophosphamide were investigated in children <2 years of age. Concentrations of cyclophosphamide and selected metabolites were determined in patients administered cyclophosphamide at doses ranging from 100–1500 mg/m2 (5–75 mg/kg), with various infusion times as determined by the standard treatment regimen that each patient was receiving. Polymorphisms in genes including CYP2B6 and CYP2C19 were investigated. Data generated for cyclophosphamide were analysed using a previously published population pharmacokinetic model. Cyclophosphamide pharmacokinetics was assessed in 111 samples obtained from 25 patients ranging from 4–23 months of age. The average cyclophosphamide clearance for the patients was 46.6 mL/min/m2 (ranging from 9.4–153 mL/min/m2), with marked inter-patient variability observed (CV 41%). No significant differences in cyclophosphamide clearance or exposure (AUC) were observed between patient groups as separated by age or body weight. However, marked differences in drug clearance and metabolism were noted between the current data in children <2 years of age and recently published results from a comparable study conducted by our group in older children, which reported significantly lower cyclophosphamide clearance values and metabolite exposures using the same population pharmacokinetic model for analysis. Whilst this study demonstrates no significant differences in cyclophosphamide clearance in patients <2 years, it highlights large differences in dosing protocols across tumour types. Furthermore, the study suggests marked differences in cyclophosphamide clearance in children less than two years of age as compared to older patients.

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