Cefepime in intensive care unit patients: Validation of a population pharmacokinetic approach and influence of covariables

2008 ◽  
Vol 46 (04) ◽  
pp. 157-164 ◽  
Author(s):  
B. Georges ◽  
J.-M. Conil ◽  
T. Seguin ◽  
E. Dieye ◽  
P. Cougot ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Approach

scholarly journals Population Pharmacokinetic Model and Pharmacokinetic Target Attainment of Micafungin in Intensive Care Unit Patients

2017 ◽  
Vol 56 (10) ◽  
pp. 1197-1206 ◽  
Author(s):  
Lisa C. Martial ◽  
Rob ter Heine ◽  
Jeroen A. Schouten ◽  
Nicole G. Hunfeld ◽  
Henk J. van Leeuwen ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Population Pharmacokinetic ◽  
Target Attainment

scholarly journals Population Pharmacokinetics of Ceftazidime in Intensive Care Unit Patients: Influence of Glomerular Filtration Rate, Mechanical Ventilation, and Reason for Admission

2009 ◽  
Vol 53 (10) ◽  
pp. 4483-4489 ◽  
Author(s):  
Bernard Georges ◽  
Jean-Marie Conil ◽  
Thierry Seguin ◽  
Stéphanie Ruiz ◽  
Vincent Minville ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Mechanical Ventilation ◽  
Intensive Care ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Pharmacokinetic Model ◽  
Volume Of Distribution ◽  
Population Pharmacokinetic ◽  
Reason For Admission

ABSTRACT The aim of this study was to develop a population-pharmacokinetic model of ceftazidime in intensive care unit patients to include the influence of patients' characteristics on the pharmacokinetics. Forty-nine patients for model building and 23 patients for validation were included in a randomized study. They received ceftazidime at 2 g three times a day or as 6 g per day continuously. A NONMEM pharmacokinetic model was constructed, and the influences of covariates were studied. The model was validated by a comparison of the predicted and observed concentrations. A final model was elaborated from the whole population. Total clearance (CL) was significantly correlated with the glomerular filtration rate (GFR) calculated by modification of the diet in renal disease (MDRD), the central volume of distribution (V1) with intubation, and the peripheral volume of distribution (V2) with the reason for admission. The mean pharmacokinetic parameters were as follows: CL, 5.48 liters/h, 40%; V1, 10.48 liters, 34%; V2, 32.12 liters, 59%; total volume, 42.60 liters, 45%; and intercompartmental clearance, 16.19 liters/h, 42%. In the polytrauma population (mechanically ventilated), the time above the MIC at steady state never corresponds to 100% for discontinuous administration, and the target concentration of five times the MIC was reached with a 6-g/day dose only for patients with an MDRD of <150 ml/min. We showed that the GFR-MDRD, mechanical ventilation, and the reason for admission may influence the achieved concentrations of ceftazidime. Our model allows the a priori dosing to be adjusted to the individual patient.

scholarly journals Vancomycin dosing assessment in intensive care unit patients based on a population pharmacokinetic/pharmacodynamic simulation

2010 ◽  
Vol 70 (2) ◽  
pp. 201-212 ◽  
Author(s):  
Natalia Revilla ◽  
Ana Martín-Suárez ◽  
Marta Paz Pérez ◽  
Félix Martín González ◽  
María del Mar Fernández de Gatta
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Population Pharmacokinetic

scholarly journals External Evaluation of Population Pharmacokinetic Models of Vancomycin in Large Cohorts of Intensive Care Unit Patients

2019 ◽  
Vol 63 (5) ◽  
Author(s):  
Tingjie Guo ◽  
Reinier M. van Hest ◽  
Luca F. Roggeveen ◽  
Lucas M. Fleuren ◽  
Patrick J. Thoral ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Prediction Error ◽  
Predictive Performance ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Models ◽  
Icu Patients ◽  
Standard Dosage ◽  
Pubmed Database ◽  
Sdr Model

ABSTRACT Dosing of vancomycin is often guided by therapeutic drug monitoring and population pharmacokinetic models in the intensive care unit (ICU). The validity of these models is crucial, as ICU patients have marked pharmacokinetic variability. Therefore, we set out to evaluate the predictive performance of published population pharmacokinetic models of vancomycin in ICU patients. The PubMed database was used to search for population pharmacokinetic models of vancomycin in adult ICU patients. The identified models were evaluated in two independent data sets which were collected from two large hospitals in the Netherlands (Amsterdam UMC, Location VUmc, and OLVG Oost). We also tested a one-compartment model with fixed values for clearance and volume of distribution, in which a clinical standard dosage regimen (SDR) was mimicked to assess its predictive performance. Prediction error was calculated to assess the predictive performance of the models. Six models plus the SDR model were evaluated. The model of Roberts et al. (J. A. Roberts, F. S. Taccone, A. A. Udy, J.-L. Vincent, F. Jacobs, and J. Lipman, Antimicrob Agents Chemother 55:2704–2709, 2011, https://doi.org/10.1128/AAC.01708-10) performed satisfactorily, with mean and median values of prediction error of 5.1% and −7.5%, respectively, for Amsterdam UMC, Location VUmc, patients, and −12.6% and −17.2% respectively, for OLVG Oost patients. The other models, including the SDR model, yielded high mean values (−49.7% to 87.7%) and median values (−56.1% to 66.1%) for both populations. In conclusion, only the model of Roberts et al. was able to validly predict the concentrations of vancomycin for our data, whereas other models and standard dosing were largely inadequate. Extensive evaluation should precede the adoption of any model in clinical practice for ICU patients.

Phenobarbital in intensive care unit pediatric population: predictive performances of population pharmacokinetic model

2017 ◽  
Vol 31 (5) ◽  
pp. 558-566 ◽  
Author(s):  
Amélie Marsot ◽  
Fabrice Michel ◽  
Estelle Chasseloup ◽  
Olivier Paut ◽  
Romain Guilhaumou ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Pediatric Population ◽  
Population Pharmacokinetic

scholarly journals Population pharmacokinetic analysis of doripenem for Japanese patients in intensive care unit

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ko Nonoshita ◽  
Yosuke Suzuki ◽  
Ryota Tanaka ◽  
Tetsuya Kaneko ◽  
Yoshifumi Ohchi ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Population Analysis ◽  
Compartment Model ◽  
Japanese Patients ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Analysis Model ◽  
Mixed Effects Modeling

AbstractWe aimed to construct a novel population pharmacokinetics (PPK) model of doripenem (DRPM) for Japanese patients in intensive care unit, incorporating the clearance of DRPM by continuous renal replacement therapy (CRRT). Twenty-one patients treated with DRPM (0.25 or 0.5 g) by intravenous infusion over 1 h were included in the study. Nine of the 21 patients were receiving CRRT. Plasma samples were obtained before and 1, 2, 4, 6 and 8 h after the first DRPM administration. PPK analysis was conducted by nonlinear mixed effects modeling using a two-compartment model. Total clearance (CLtotal) in the model was divided into CRRT clearance (CLCRRT) and body clearance (CLbody). The final model was: CLtotal (L h−1) = CLbody(non-CRRT) = 3.65 × (Ccr/62.25)0.64 in the absence of CRRT, or = CLbody(CRRT) + CLCRRT = 2.49 × (Ccr/52.75)0.42 + CLCRRT in the presence of CRRT; CLCRRT = QE × 0.919 (0.919 represents non-protein binding rate of DRPM); V1 (L) = 10.04; V2 (L) = 8.13; and Q (L h−1) = 3.53. Using this model, CLtotal was lower and the distribution volumes (V1 and V2) tended to be higher compared to previous reports. Also, Ccr was selected as a significant covariate for CLbody. Furthermore, the contribution rate of CLCRRT to CLtotal was 30–40%, suggesting the importance of drug removal by CRRT. The population analysis model used in this study is a useful tool for planning DRPM regimen and administration. Our novel model may contribute greatly to proper use of DRPM in patients requiring intensive care.

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