Modeling Population Pharmacokinetics of Lidocaine

2001 ◽  
Vol 94 (4) ◽  
pp. 566-573 ◽  
Author(s):  
Jette A. Kuipers ◽  
Fred Boer ◽  
Annemiek de Roode ◽  
Erik Olofsen ◽  
James G. Bovill ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Pharmacokinetic Model ◽  
Population Pharmacokinetic ◽  
Ratio Test ◽  
Pharmacokinetic Models ◽  
Population Pharmacokinetic Modeling ◽  
Population Pharmacokinetic Study ◽  
Electrical Bioimpedance ◽  
Demographic Covariates ◽  
The Individual

Background Inclusion of cardiac output and other physiologic parameters, in addition to or instead of, demographic variables might improve the population pharmacokinetic modeling of lidocaine. Methods Thirty-one patients were included in a population pharmacokinetic study of lidocaine. After bolus injection of lidocaine (1 mg/kg), 22 or 10 blood samples per patient were taken from a radial artery. During the experiment, cardiac output was measured using a thoracic electrical bioimpedance method. The following four population pharmacokinetic models were constructed and their performances investigated: a model with no covariates, a model with cardiac output as covariate, a model with demographic covariates, and a model with both cardiac output and demographic characteristics as covariates. Model discrimination was performed with the likelihood ratio test. Results Inclusion of cardiac output resulted in a significant improvement of the pharmacokinetic model, but inclusion of demographic covariates was even better. However, the best model was obtained by inclusion of both demographic covariates and cardiac output in the pharmacokinetic model. Conclusions When population pharmacokinetic models are used for individualization of dosing schedules, physiologic covariates, e.g., cardiac output, can improve their ability to predict the individual kinetics.

scholarly journals Population Pharmacokinetic Study of Prophylactic Fluconazole in Preterm Infants for Prevention of Invasive Candidiasis

2019 ◽  
Vol 63 (6) ◽  
Author(s):  
Yu Kyong Kim ◽  
Juyoung Lee ◽  
Jaeseong Oh ◽  
Su-jin Rhee ◽  
Seung Han Shin ◽  
...  
Keyword(s):  
Body Weight ◽  
Preterm Infants ◽  
Goodness Of Fit ◽  
Pharmacokinetic Model ◽  
Dose Interval ◽  
Volume Of Distribution ◽  
Population Pharmacokinetic ◽  
Oral Fluconazole ◽  
Systemic Fungal Infection ◽  
Population Pharmacokinetic Study

ABSTRACT Fluconazole is an antifungal agent with reported evidence for its prophylactic effect against systemic fungal infection in preterm infants. The aim of this study was to build a population pharmacokinetic model to evaluate the pharmacokinetic characteristics of intravenous and oral fluconazole in preterm infants with the current prophylactic fluconazole dosing regimen. A pharmacokinetic model was developed using 301 fluconazole concentrations from 75 preterm infants with a baseline body weight (WT) ranging from 0.5 to 1.5 kg and an estimated glomerular filtration rate (eGFR) ranging from 12.9 to 58.5 ml/min/1.73 m2. Eligible infants received an intravenous or oral dose of 3 mg/kg of body weight of fluconazole, twice weekly with a ≥72-h dose interval, for 4 weeks. The model was qualified with basic goodness-of-fit diagnostics, visual predictive checks, and bootstrapping. The fluconazole pharmacokinetics was well described with a one-compartment linear model with a proportional residual error. The population clearance (CL) and volume of distribution (V) were derived as 0.0197 × (WT/1.00)0.746 × (eGFR/25.0)0.463 × exp(η) and 1.04 × WT × exp(η), respectively. Such covariate analyses augment the awareness of the need for personalized dosing in preterm infants. (This study has been registered at ClinicalTrials.gov under identifier NCT01683760.)

scholarly journals A Population Pharmacokinetic Model to Predict the Individual Starting Dose of Tacrolimus Following Pediatric Renal Transplantation

2017 ◽  
Vol 57 (4) ◽  
pp. 475-489 ◽  
Author(s):  
Louise M. Andrews ◽  
Dennis A. Hesselink ◽  
Teun van Gelder ◽  
Birgit C. P. Koch ◽  
Elisabeth A. M. Cornelissen ◽  
...  
Keyword(s):  
Renal Transplantation ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Population Pharmacokinetic ◽  
Pediatric Renal Transplantation ◽  
Starting Dose ◽  
The Individual

scholarly journals Population Pharmacokinetic Analysis of Cefaclor in Healthy Korean Subjects

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 754
Author(s):  
Seung-Hyun Jeong ◽  
Ji-Hun Jang ◽  
Hea-Young Cho ◽  
Yong-Bok Lee
Keyword(s):  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Factors Affecting ◽  
Population Pharmacokinetic Study ◽  
Final Population ◽  
Subject Variability

The aims of this study were: (1) to perform population pharmacokinetic analysis of cefaclor in healthy Korean subjects, and (2) to investigate possible effects of various covariates on pharmacokinetic parameters of cefaclor. Although cefaclor belongs to the cephalosporin family antibiotic that has been used in various indications, there have been very few population studies on factors affecting its pharmacokinetics. Therefore, this study is very important in that effective therapy could be possible through a population pharmacokinetic study that explores effective covariates related to cefaclor pharmacokinetic diversity between individuals. Pharmacokinetic results of 48 subjects with physical and biochemical parameters were used for the population pharmacokinetic analysis of cefaclor. A one-compartment with lag-time and first-order absorption/elimination was constructed as a base model and extended to include covariates that could influence between-subject variability. Creatinine clearance and body weight significantly influenced systemic clearance and distribution volume of cefaclor. Cefaclor’s final population pharmacokinetic model was validated and some of the population’s pharmacokinetic diversity could be explained. Herein, we first describe the establishment of a population pharmacokinetic model of cefaclor for healthy Koreans that might be useful for customizing cefaclor or exploring additional covariates in patients.

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

2015 ◽  
Vol 60 (2) ◽  
pp. 1013-1021 ◽  
Author(s):  
Esther J. H. Janssen ◽  
Pyry A. J. Välitalo ◽  
Karel Allegaert ◽  
Roosmarijn F. W. de Cock ◽  
Sinno H. P. Simons ◽  
...  
Keyword(s):  
Pediatric Population ◽  
External Validation ◽  
Population Pharmacokinetic ◽  
Target Area ◽  
Pharmacokinetic Models ◽  
Time Curve ◽  
Population Pharmacokinetic Modeling ◽  
Model Based ◽  
Dosing Algorithm ◽  
Dosing Regimens

ABSTRACTBecause 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 (AUC24/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.

scholarly journals Bioequivalence and Population Pharmacokinetic Modeling of Two Forms of Antibiotic, Cefuroxime Lysine and Cefuroxime Sodium, after Intravenous Infusion in Beagle Dogs

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Longshan Zhao ◽  
Qing Li ◽  
Xingang Li ◽  
Ran Yin ◽  
Xiaohui Chen ◽  
...  
Keyword(s):  
Intravenous Infusion ◽  
Dose Range ◽  
Relative Bioavailability ◽  
Individual Variability ◽  
Population Pharmacokinetic ◽  
Beagle Dogs ◽  
Population Pharmacokinetic Modeling ◽  
Population Pharmacokinetic Study ◽  
Basic Model ◽  
Significant Difference

To investigate the bioequivalence and the population pharmacokinetics of cefuroxime lysine and cefuroxime sodium in healthy beagle dogs. A randomized 2-period crossover design in 18 healthy beagle dogs after receiving 20, 40, and 80 mg/kg of cefuroxime lysine or cefuroxime sodium was conducted. A 3-compartment open model was used as the basic model for the population pharmacokinetic study. Both of the antibiotics exhibited dose-proportional pharmacokinetics over the dose range of 20–80 mg/kg. The mean relative bioavailability of cefuroxime lysine versus cefuroxime sodium was 1.05 (range, 0.71 to 1.42), with a significant difference between males and females. The estimates of population pharmacokinetic of CL,V1,Q2,V2,Q3,V3were 3.74 mL/h, 1.70 mL, 29.5 mL/min, 3.58 mL, 0.31 mL/min, and 158 mL for cefuroxime lysine and 4.10 mL/h, 1.00 mL, 38.5 mL/min, 4.19 mL, 0.06 mL/min, and 13.6 mL for cefuroxime sodium, respectively. The inter-individual variability was determined to be less than 29.1%. A linear pharmacokinetic was revealed for cefuroxime lysine and cefuroxime sodium in dogs after intravenous infusion, and the bioequivalence of these forms of the antibiotic was observed with the significant gender-related differences in mean relative bioavailability of cefuroxime lysine versus cefuroxime sodium.

scholarly journals Evaluation of the Predictive Performance of Population Pharmacokinetic Models of Adalimumab in Patients with Inflammatory Bowel Disease

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1244
Author(s):  
Silvia Marquez-Megias ◽  
Amelia Ramon-Lopez ◽  
Patricio Más-Serrano ◽  
Marcos Diaz-Gonzalez ◽  
Maria Remedios Candela-Boix ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Predictive Performance ◽  
Stochastic Simulations ◽  
University Hospital ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Models ◽  
Inflammatory Bowel ◽  
The Individual

Adalimumab is a monoclonal antibody used for inflammatory bowel disease. Due to its considerably variable pharmacokinetics, the loss of response and the development of anti-antibodies, it is highly recommended to use a model-informed precision dosing approach. The aim of this study is to evaluate the predictive performance of different population-pharmacokinetic models of adalimumab for inflammatory bowel disease to determine the pharmacokinetic model(s) that best suit our population to use in the clinical routine. A retrospective observational study with 134 patients was conducted at the General University Hospital of Alicante between 2014 and 2019. Model adequacy of each model was evaluated by the distribution of the individual pharmacokinetic parameters and the NPDE plots whereas predictive performance was assessed by calculating bias and precision. Moreover, stochastic simulations were performed to optimize the maintenance doses in the clinical protocols, to reach the target of 8 mg/L in at least 75% of the population. Two population-pharmacokinetic models were selected out of the six found in the literature which performed better in terms of adequacy and predictive performance. The stochastic simulations suggested the benefits of increasing the maintenance dose in protocol to reach the 8 mg/L target.

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 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 Population Pharmacokinetics with Monte Carlo Simulations of Gentamicin in a Population of Severely Ill Adult Patients from Sub-Saharan Africa

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Jeannet C. Bos ◽  
Jan M. Prins ◽  
Mabor C. Mistício ◽  
Ginto Nunguiane ◽  
Cláudia N. Lang ◽  
...  
Keyword(s):  
Pharmacokinetic Model ◽  
Sub Saharan Africa ◽  
Population Pharmacokinetic ◽  
Once Daily ◽  
Population Pharmacokinetic Study ◽  
Mixed Effects Modeling ◽  
Substantial Risk ◽  
Severe Infections ◽  
Sub Saharan ◽  
Pharmacodynamic Data

ABSTRACT In sub-Saharan Africa (SSA), gentamicin is commonly used for severe infections in non-intensive-care-unit (ICU) settings, but pharmacokinetic and pharmacodynamic data for this specific population are lacking. We performed a population pharmacokinetic study in an adult Mozambican non-ICU hospital population treated with gentamicin (n = 48) and developed a pharmacokinetic model using nonlinear mixed-effects modeling. Simulations showed that non-ICU patient populations in SSA may be at substantial risk for underexposure to gentamicin during routine once-daily dosing.

Sign in / Sign up

Export Citation Format

Share Document