scholarly journals Assessing the predictive performance of population pharmacokinetic models for intravenous polymyxin B in critically ill patients

2021 ◽  
Author(s):  
Patrick O. Hanafin ◽  
Roger L. Nation ◽  
Marc H. Scheetz ◽  
Alexandre P. Zavascki ◽  
Ana M. Sandri ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Predictive Performance ◽  
Polymyxin B ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Models

scholarly journals Amikacin Initial Dose in Critically Ill Patients: a Nonparametric Approach To Optimize A Priori Pharmacokinetic/Pharmacodynamic Target Attainments in Individual Patients

2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Clément Boidin ◽  
Laurent Bourguignon ◽  
Sabine Cohen ◽  
Claire Roger ◽  
Jean-Yves Lefrant ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
A Priori ◽  
Predictive Performance ◽  
Compartment Model ◽  
Population Pharmacokinetic ◽  
Time Curve ◽  
Data Set ◽  
Nonparametric Approach ◽  
The Right

ABSTRACT Amikacin is commonly used for probabilistic antimicrobial therapy in critically ill patients with sepsis. Its narrow therapeutic margin makes it challenging to determine the right individual dose that ensures the highest efficacy target attainment rate (TAR) in this setting. This study aims to develop a new initial dosing approach for amikacin by optimizing the a priori TAR in this population. A population pharmacokinetic model was built with a learning data set from critically ill patients who received amikacin. It was then used to design an initial dosing approach maximizing a priori TAR for a target ratio of ≥8 for the peak concentration to the MIC (Cmax/MIC) or of ≥75 for the ratio of the area under the concentration-time curve from 0 to 24 h to the MIC (AUC0–24/MIC). In the 166 patients included, 53% had amikacin Cmax of ≥64 mg/liter with a median dose of 23.4 mg/kg. A two-compartment model with creatinine clearance and body surface area as covariates best described the data and showed good predictive performance. Our dosing approach was successful in optimizing TAR for Cmax/MIC, with a rate of 92.9% versus 67.9% using a 30-mg/kg regimen, based on an external subset of data and assuming a MIC of 8 mg/liter. Mean optimal doses were higher (3.5 ± 0.5 g) than with the 30-mg/kg regimen (2.1 ± 0.3 g). Suggested doses varied with the MIC, the target index, and desired TAR threshold. A dosing algorithm based on the method is proposed for a large range of patient covariates. Clinical studies are necessary to confirm efficacy and safety of this optimized dosing approach.

scholarly journals Comparison of the Accuracy and Precision of Pharmacokinetic Equations To Predict Free Meropenem Concentrations in Critically Ill Patients

2014 ◽  
Vol 59 (3) ◽  
pp. 1411-1417 ◽  
Author(s):  
Gloria Wong ◽  
Andras Farkas ◽  
Rachel Sussman ◽  
Gergely Daroczi ◽  
William W. Hope ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Prediction Performance ◽  
Population Pharmacokinetic ◽  
Clinical Implications ◽  
Pharmacokinetic Models ◽  
Accuracy And Precision ◽  
Absolute Bias ◽  
Dose Change ◽  
Separate Cohort

ABSTRACTPopulation pharmacokinetic analyses can be applied to predict optimized dosages for individual patients. The aim of this study was to compare the prediction performance of the published population pharmacokinetic models for meropenem in critically ill patients. We coded the published population pharmacokinetic models with covariate relationships into dosing software to predict unbound meropenem concentrations measured in a separate cohort of critically ill patients. The agreements between the observed and predicted concentrations were evaluated with Bland-Altman plots. The absolute and relative bias and precision of the models were determined. The clinical implications of the results were evaluated according to whether dose adjustments were required from the predictions to achieve a meropenem concentration of >2 mg/liter throughout the dosing interval. A total of 157 free meropenem concentrations from 56 patients were analyzed. Eight published population pharmacokinetic models were compared. The models showed an absolute bias in predicting the unbound meropenem concentrations from a mean percent difference (95% confidence interval [CI]) of −108.5% (−119.9% to −97.3%) to 19.9% (7.3% to 32.7%), while absolute precision ranged from −249.1% (−263.4% to −234.8%) to 31.9% (17.6% to 46.2%) and −178.9% (−196.9% to −160.9%) to 175.0% (157.0% to 193.0%). A dose change was required in 44% to 64% of the concentration results. Seven of the eight equations evaluated underpredicted free meropenem concentrations. In conclusion, the overall accuracy of these models supports their inclusion in dosing software and application for individualizing meropenem doses in critically ill patients to increase the likelihood of achievement of optimal antibiotic exposures.

scholarly journals Parametric and Nonparametric Population Pharmacokinetic Models to Assess Probability of Target Attainment of Imipenem Concentrations in Critically Ill Patients

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2170
Author(s):  
Femke de Velde ◽  
Brenda C. M. de Winter ◽  
Michael N. Neely ◽  
Jan Strojil ◽  
Walter M. Yamada ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
External Validation ◽  
Predictive Performance ◽  
Nonparametric Model ◽  
Population Pharmacokinetic ◽  
Target Attainment ◽  
Population Pharmacokinetic Modeling ◽  
Nonparametric Models ◽  
Dosing Regimens

Population pharmacokinetic modeling and simulation (M&S) are used to improve antibiotic dosing. Little is known about the differences in parametric and nonparametric M&S. Our objectives were to compare (1) the external validation of parametric and nonparametric models of imipenem in critically ill patients and (2) the probability of target attainment (PTA) calculations using simulations of both models. The M&S software used was NONMEM 7.2 (parametric) and Pmetrics 1.5.2 (nonparametric). The external predictive performance of both models was adequate for eGFRs ≥ 78 mL/min but insufficient for lower eGFRs, indicating that the models (developed using a population with eGFR ≥ 60 mL/min) could not be extrapolated to lower eGFRs. Simulations were performed for three dosing regimens and three eGFRs (90, 120, 150 mL/min). Fifty percent of the PTA results were similar for both models, while for the other 50% the nonparametric model resulted in lower MICs. This was explained by a higher estimated between-subject variability of the nonparametric model. Simulations indicated that 1000 mg q6h is suitable to reach MICs of 2 mg/L for eGFRs of 90–120 mL/min. For MICs of 4 mg/L and for higher eGFRs, dosing recommendations are missing due to largely different PTA values per model. The consequences of the different modeling approaches in clinical practice should be further investigated.

scholarly journals Performance of Population Pharmacokinetic Models in Predicting Polymyxin B Exposures

2020 ◽  
Vol 8 (11) ◽  
pp. 1814
Author(s):  
Vincent Tam ◽  
Lawrence Lee ◽  
Tat-Ming Ng ◽  
Tze-Peng Lim ◽  
Benjamin Cherng ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Area Under The Curve ◽  
Predictive Performance ◽  
Total Body Weight ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Patient Specific ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Models

Polymyxin B is the last line of defense in treating multidrug-resistant gram-negative bacterial infections. Dosing of polymyxin B is currently based on total body weight, and a substantial intersubject variability has been reported. We evaluated the performance of different population pharmacokinetic models to predict polymyxin B exposures observed in individual patients. In a prospective observational study, standard dosing (mean 2.5 mg/kg daily) was administered in 13 adult patients. Serial blood samples were obtained at steady state, and plasma polymyxin B concentrations were determined by a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The best-fit estimates of clearance and daily doses were used to derive the observed area under the curve (AUC) in concentration–time profiles. For comparison, 5 different population pharmacokinetic models of polymyxin B were conditioned using patient-specific dosing and demographic (if applicable) variables to predict polymyxin B AUC of the same patient. The predictive performance of the models was assessed by the coefficient of correlation, bias, and precision. The correlations between observed and predicted AUC in all 5 models examined were poor (r2 < 0.2). Nonetheless, the models were reasonable in capturing AUC variability in the patient population. Therapeutic drug monitoring currently remains the only viable approach to individualized dosing.

Evaluation of population pharmacokinetic models for amikacin dosage individualization in critically ill patients

2009 ◽  
Vol 61 (6) ◽  
pp. 759-766 ◽  
Author(s):  
María del Mar Fernández de Gatta ◽  
Silvia Romano Moreno ◽  
María Victoria Calvo ◽  
Ramón Ardanuy ◽  
Alfonso Domínguez-Gil ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Models

Evaluation of population pharmacokinetic models for amikacin dosage individualization in critically ill patients

2009 ◽  
Vol 61 (6) ◽  
pp. 759-766 ◽  
Author(s):  
María del Mar Fernández de Gatta ◽  
Silvia Romano Moreno ◽  
María Victoria Calvo ◽  
Ramón Ardanuy ◽  
Alfonso Domínguez-Gil ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Models

scholarly journals Novel Population Pharmacokinetic Model for Linezolid in Critically Ill Patients and Evaluation of the Adequacy of the Current Dosing Recommendation

Pharmaceutics ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 54 ◽  
Author(s):  
Amaia Soraluce ◽  
Helena Barrasa ◽  
Eduardo Asín-Prieto ◽  
Jose Ángel Sánchez-Izquierdo ◽  
Javier Maynar ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Standard Dose ◽  
Compartment Model ◽  
Antimicrobial Treatment ◽  
Population Pharmacokinetic ◽  
Renal Replacement Therapies ◽  
Continuous Renal Replacement Therapies

Antimicrobial treatment in critically ill patients remains challenging. The aim of this study was to develop a population pharmacokinetic model for linezolid in critically ill patients and to evaluate the adequacy of current dosing recommendation (600 mg/12 h). Forty inpatients were included, 23 of whom were subjected to continuous renal replacement therapies (CRRT). Blood and effluent samples were drawn after linezolid administration at defined time points, and linezolid levels were measured. A population pharmacokinetic model was developed, using NONMEM 7.3. The percentage of patients that achieved the pharmacokinetic/pharmacodynamic (PK/PD) targets was calculated (AUC24/MIC > 80 and 100% T>MIC). A two-compartment model best described the pharmacokinetics of linezolid. Elimination was conditioned by the creatinine clearance and by the extra-corporeal clearance if the patient was subjected to CRRT. For most patients, the standard dose of linezolid did not cover infections caused by pathogens with MIC ≥ 2 mg/L. Continuous infusion may be an alternative, especially when renal function is preserved.

Sign in / Sign up

Export Citation Format

Share Document