External evaluation of a published population pharmacokinetic model of valproic acid in Thai manic patients

Objective This prospective study aimed to establish the valproic acid (VPA) population pharmacokinetic model in Chinese patients and realise personalised medication on the basis of population pharmacokinetics. Methods The patients’ clinical information and VPA plasma concentrations were collected from The General Hospital of Taiyuan Iron & Steel (Group) Corporation (TISCO). Nonlinear mixed-effect modelling was used to build the population pharmacokinetic model. To characterise the pharmacokinetic data, a one-compartment pharmacokinetic model with first-order absorption and elimination was used. The first-order conditional estimation with η-ε interaction was applied throughout the model-developing procedure. The absorption rate constant (Ka) was fixed at 2.38 hour−1, and the impact of covariates on clearance and apparent volume of distribution were also explored. Medical records of 60 inpatients were reviewed prospectively and the objective function value (OFV) of the base model and final model were 851.813 and 817.622, respectively. Results Gender was identified as the covariate that had a significant impact on the volume of distribution, and albumin and CYP2C19 genotypes influenced clearance. Conclusion Bootstrap and VPC indicated that a reliable model had been developed that was based on the simulation results, and a simple-to-use dosage regimen table was created to guide clinicians for VPA drug dosing.

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01908-21 ◽

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).…

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00669-18 ◽

2018 ◽

Vol 62 (9) ◽

Cited By ~ 2

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.

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00205-17 ◽

2017 ◽

Vol 61 (8) ◽

Cited By ~ 7

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.

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