Faculty Opinions recommendation of An evaluation of using population pharmacokinetic models to estimate pharmacodynamic parameters for propofol and bispectral index in children.

2011 ◽  
Author(s):  
Valerie Billard
Keyword(s):  
Bispectral Index ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Models

scholarly journals An Evaluation of Using Population Pharmacokinetic Models to Estimate Pharmacodynamic Parameters for Propofol and Bispectral Index in Children

2011 ◽  
Vol 115 (1) ◽  
pp. 83-93 ◽  
Author(s):  
Marc J. Coppens ◽  
Douglas J. Eleveld ◽  
Johannes H. Proost ◽  
Luc A. M. Marks ◽  
Jan F. P. Van Bocxlaer ◽  
...  
Keyword(s):  
Objective Function ◽  
Bispectral Index ◽  
Pharmacokinetic Model ◽  
Dental Treatment ◽  
Venous Blood ◽  
Plasma Concentrations ◽  
Accurate Estimation ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Models ◽  
Objective Function Values

Background To study propofol pharmacodynamics in a clinical setting a pharmacokinetic model must be used to predict drug plasma concentrations. Some investigators use a population pharmacokinetic model from existing literature and minimize the pharmacodynamic objective function. The purpose of the study was to determine whether this method selects the best-performing pharmacokinetic model in a set and provides accurate estimates of pharmacodynamic parameters in models for bispectral index in children after propofol administration. Methods Twenty-eight children classified as American Society of Anesthesiologists physical status 1 who were given general anesthesia for dental treatment were studied. Anesthesia was given using target-controlled infusion of propofol based on the Kataria model. Propofol target plasma concentration was 7 μg/ml for 15 min, followed by 1 μg/ml for 15 min or until signs of awakening, followed by 5 μg/ml for 15 min. Venous blood samples were taken 1, 2, 5, 10, and 15 min after each change in target. A classic pharmacokinetic-pharmacodynamic model was estimated, and the methodology of other studies was duplicated using pharmacokinetic models from the literature and (re-)estimating the pharmacodynamic models. Results There is no clear relationship between pharmacokinetic precision and the pharmacodynamic objective function. Low pharmacodynamic objective function values are not associated with accurate estimation of the pharmacodynamic parameters when the pharmacokinetic model is taken from other sources. Conclusion Minimization of the pharmacodynamic objective function does not select the most accurate pharmacokinetic model. Using population pharmacokinetic models from the literature instead of the 'true' pharmacokinetic model can lead to better predictions of bispectral index while incorrectly estimating the pharmacodynamic parameters.

scholarly journals External Evaluation of Population Pharmacokinetic Models and Bayes-Based Dosing of Infliximab

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1191
Author(s):  
Celine Konecki ◽  
Catherine Feliu ◽  
Yoann Cazaubon ◽  
Delphine Giusti ◽  
Marcelle Tonye-Libyh ◽  
...  
Keyword(s):  
Goodness Of Fit ◽  
Inflammatory Diseases ◽  
Plasma Concentrations ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Models ◽  
External Evaluation ◽  
Immunomodulatory Treatment ◽  
Weighted Residuals ◽  
Prediction Distribution ◽  
Target Plasma

Despite the well-demonstrated efficacy of infliximab in inflammatory diseases, treatment failure remains frequent. Dose adjustment using Bayesian methods has shown in silico its interest in achieving target plasma concentrations. However, most of the published models have not been fully validated in accordance with the recommendations. This study aimed to submit these models to an external evaluation and verify their predictive capabilities. Eight models were selected for external evaluation, carried out on an independent database (409 concentrations from 157 patients). Each model was evaluated based on the following parameters: goodness-of-fit (comparison of predictions to observations), residual error model (population weighted residuals (PWRES), individual weighted residuals (IWRES), and normalized prediction distribution errors (NPDE)), and predictive performances (prediction-corrected visual predictive checks (pcVPC) and Bayesian simulations). The performances observed during this external evaluation varied greatly from one model to another. The eight evaluated models showed a significant bias in population predictions (from −7.19 to 7.38 mg/L). Individual predictions showed acceptable bias and precision for six of the eight models (mean error of −0.74 to −0.29 mg/L and mean percent error of −16.6 to −0.4%). Analysis of NPDE and pcVPC confirmed these results and revealed a problem with the inclusion of several covariates (weight, concomitant immunomodulatory treatment, presence of anti-drug antibodies). This external evaluation showed satisfactory results for some models, notably models A and B, and highlighted several prospects for improving the pharmacokinetic models of infliximab for clinical-biological application.

External evaluation of published population pharmacokinetic models of polymyxin B

2021 ◽  
Author(s):  
Ya-qian Li ◽  
Kai-feng Chen ◽  
Jun-jie Ding ◽  
Hong-yi Tan ◽  
Nan Yang ◽  
...  
Keyword(s):  
Polymyxin B ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Models ◽  
External Evaluation

scholarly journals External evaluation of population pharmacokinetic models for ciclosporin in adult renal transplant recipients

2017 ◽  
Vol 84 (1) ◽  
pp. 153-171 ◽  
Author(s):  
Jun-Jun Mao ◽  
Zheng Jiao ◽  
Hwi-Yeol Yun ◽  
Chen-Yan Zhao ◽  
Han-Chao Chen ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Population Pharmacokinetic ◽  
Renal Transplant Recipients ◽  
Pharmacokinetic Models ◽  
Transplant Recipients ◽  
External Evaluation

scholarly journals Pharmacokinetics-Pharmacodynamics of Gatifloxacin in a Lethal Murine Bacillus anthracis Inhalation Infection Model

2007 ◽  
Vol 51 (12) ◽  
pp. 4351-4355 ◽  
Author(s):  
Paul G. Ambrose ◽  
Alan Forrest ◽  
William A. Craig ◽  
Chistopher M. Rubino ◽  
Sujata M. Bhavnani ◽  
...  
Keyword(s):  
Bacillus Anthracis ◽  
Survival Data ◽  
Sensitivity Analyses ◽  
Maximum Effect ◽  
Infection Model ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Models ◽  
Concentration Time ◽  
Dosing Regimens ◽  
Adults And Children

ABSTRACT We determined the pharmacokinetic-pharmacodynamic (PK-PD) measure most predictive of gatifloxacin efficacy and the magnitude of this measure necessary for survival in a murine Bacillus anthracis inhalation infection model. We then used population pharmacokinetic models for gatifloxacin and simulation to identify dosing regimens with high probabilities of attaining exposures likely to be efficacious in adults and children. In this work, 6- to 8-week-old nonneutropenic female BALB/c mice received aerosol challenges of 50 to 75 50% lethal doses of B. anthracis (Ames strain, for which the gatifloxacin MIC is 0.125 mg/liter). Gatifloxacin was administered at 6- or 8-h intervals beginning 24 h postchallenge for 21 days, and dosing was designed to produce profiles mimicking fractionated concentration-time profiles for humans. Mice were evaluated daily for survival. Hill-type models were fitted to survival data. To identify potentially effective dosing regimens, adult and pediatric population pharmacokinetic models for gatifloxacin and Monte Carlo simulation were used to generate 5,000 individual patient exposure estimates. The ratio of the area under the concentration-time curve from 0 to 24 h (AUC0-24) to the MIC of the drug for the organism (AUC0-24/MIC ratio) was the PK-PD measure most predictive of survival (R 2 = 0.96). The 50% effective dose (ED50) and the ED90 and ED99 corresponded to AUC0-24/MIC ratios of 11.5, 15.8, and 30, respectively, where the maximum effect was 97% survival. Simulation results indicate that a daily gatifloxacin dose of 400 mg for adults and 10 mg/kg of body weight for children gives a 100% probability of attaining the PK-PD target (ED99). Sensitivity analyses suggest that the probability of PK-PD target attainment in adults and children is not affected by increases in MICs for strains of B. anthracis to levels as high as 0.5 mg/liter.

scholarly journals External validation of the predictive performance of population pharmacokinetic models for phenobarbital in pediatric patients

2020 ◽  
Author(s):  
Sunae Ryu ◽  
Woo Jin Jung ◽  
Zheng Jiao ◽  
Jung Woo Chae ◽  
Hwi-yeol Yun
Keyword(s):  
External Validation ◽  
Predictive Performance ◽  
Validation Dataset ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Models ◽  
Bayesian Forecasting ◽  
Predictive Capability ◽  
Young Infants ◽  
Simulation Based

Aim: Several studies have reported population pharmacokinetic models for phenobarbital (PB), but the predictive performance of these models has not been well documented. This study aims to do external validation of the predictive performance in published pharmacokinetic models. Methods: Therapeutic drug monitoring data collected in neonates and young infants treated with PB for seizure control, was used for external validation. A literature review was conducted through PubMed to identify population pharmacokinetic models. Prediction- and simulation-based diagnostics, and Bayesian forecasting were performed for external validation. The incorporation of size or maturity functions into the published models was also tested for prediction improvement. Results: A total of 79 serum concentrations from 28 subjects were included in the external validation dataset. Seven population pharmacokinetic studies of PB were selected for evaluation. The model by Voller et al. [27] showed the best performance concerning prediction-based evaluation. In simulation-based analyses, the normalized prediction distribution error of two models (those of Shellhaas et al. [24] and Marsot et al. [25]) obeyed a normal distribution. Bayesian forecasting with more than one observation improved predictive capability. Incorporation of both allometric size scaling and maturation function generally enhanced the predictive performance, but with marked improvement for the adult pharmacokinetic model. Conclusion: The predictive performance of published pharmacokinetic models of PB was diverse, and validation may be necessary to extrapolate to different clinical settings. Our findings suggest that Bayesian forecasting improves the predictive capability of individual concentrations for pediatrics.

Tacrolimus population pharmacokinetic models according to CYP3A5/CYP3A4/POR genotypes in Chinese Han renal transplant patients

2018 ◽  
Vol 19 (13) ◽  
pp. 1013-1025 ◽  
Author(s):  
Wan Zhu ◽  
Ling Xue ◽  
Hongwei Peng ◽  
Zhouping Duan ◽  
Xuelian Zheng ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Models ◽  
Chinese Han ◽  
Transplant Patients ◽  
Renal Transplant Patients

Development and comparison of population pharmacokinetic models of vancomycin in neurosurgical patients based on two different renal function markers

2019 ◽  
Vol 45 (1) ◽  
pp. 88-96 ◽  
Author(s):  
Li Jing ◽  
Tao‐tao Liu ◽  
Qing Guo ◽  
Ming Chen ◽  
Jie‐jiu Lu ◽  
...  
Keyword(s):  
Renal Function ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Models ◽  
Neurosurgical Patients

PKgraph: An R package for graphically diagnosing population pharmacokinetic models

2011 ◽  
Vol 104 (3) ◽  
pp. 461-471 ◽  
Author(s):  
Xiaoyong Sun ◽  
Kai Wu ◽  
Dianne Cook
Keyword(s):  
R Package ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Models
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