scholarly journals Investigating pulmonary and systemic pharmacokinetics of inhaled olodaterol in healthy volunteers using a population pharmacokinetic approach

2016 ◽  
Vol 81 (3) ◽  
pp. 538-552 ◽  
Author(s):  
Jens Markus Borghardt ◽  
Benjamin Weber ◽  
Alexander Staab ◽  
Christina Kunz ◽  
Stephan Formella ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Approach

The individualization of the infusion rate of intravenous lipid emulsion: A population pharmacokinetic approach

2018 ◽  
Vol 37 ◽  
pp. S166-S167
Author(s):  
K. Fukushima ◽  
K. Omura ◽  
S. Goshi ◽  
M. Tanaka ◽  
A. Okada ◽  
...  
Keyword(s):  
Infusion Rate ◽  
Lipid Emulsion ◽  
Population Pharmacokinetic ◽  
Intravenous Lipid Emulsion ◽  
Pharmacokinetic Approach

scholarly journals Novel Population Pharmacokinetic Approach to Explain the Differences between Cystic Fibrosis Patients and Healthy Volunteers via Protein Binding

Pharmaceutics ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 286 ◽  
Author(s):  
Nirav Shah ◽  
Jürgen Bulitta ◽  
Martina Kinzig ◽  
Cornelia Landersdorfer ◽  
Yuanyuan Jiao ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Protein Binding ◽  
Healthy Volunteers ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Population Pharmacokinetic ◽  
Unbound Fraction ◽  
Low Protein ◽  
Novel Approach ◽  
Special Patient

The pharmacokinetics in patients with cystic fibrosis (CF) has long been thought to differ considerably from that in healthy volunteers. For highly protein bound β-lactams, profound pharmacokinetic differences were observed between comparatively morbid patients with CF and healthy volunteers. These differences could be explained by body weight and body composition for β-lactams with low protein binding. This study aimed to develop a novel population modeling approach to describe the pharmacokinetic differences between both subject groups by estimating protein binding. Eight patients with CF (lean body mass [LBM]: 39.8 ± 5.4kg) and six healthy volunteers (LBM: 53.1 ± 9.5kg) received 1027.5 mg cefotiam intravenously. Plasma concentrations and amounts in urine were simultaneously modelled. Unscaled total clearance and volume of distribution were 3% smaller in patients with CF compared to those in healthy volunteers. After allometric scaling by LBM to account for body size and composition, the remaining pharmacokinetic differences were explained by estimating the unbound fraction of cefotiam in plasma. The latter was fixed to 50% in male and estimated as 54.5% in female healthy volunteers as well as 56.3% in male and 74.4% in female patients with CF. This novel approach holds promise for characterizing the pharmacokinetics in special patient populations with altered protein binding.

Population pharmacokinetic–pharmacodynamic modelling of enalapril in healthy volunteers

2007 ◽  
Vol 32 (1) ◽  
pp. S14
Author(s):  
I. Gil-Aldea ◽  
M.A. Campanero ◽  
J.R. Azanza ◽  
O. Mariscal ◽  
B. Sádaba
Keyword(s):  
Healthy Volunteers ◽  
Population Pharmacokinetic ◽  
Pharmacodynamic Modelling

scholarly journals Pharmacokinetic Modeling and Limited Sampling Strategies Based on Healthy Volunteers for Monitoring of Ertapenem in Patients with Multidrug-Resistant Tuberculosis

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
S. P. van Rijn ◽  
M. A. Zuur ◽  
R. van Altena ◽  
O. W. Akkerman ◽  
J. H. Proost ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Sampling Strategy ◽  
Free Fraction ◽  
Limited Sampling Strategy ◽  
Population Pharmacokinetic ◽  
Time Curve ◽  
Limited Sampling ◽  
Mdr Tb

ABSTRACT Ertapenem is a broad-spectrum carbapenem antibiotic whose activity against Mycobacterium tuberculosis is being explored. Carbapenems have antibacterial activity when the plasma concentration exceeds the MIC at least 40% of the time (40% T MIC). To assess the 40% T MIC in multidrug-resistant tuberculosis (MDR-TB) patients, a limited sampling strategy was developed using a population pharmacokinetic model based on data for healthy volunteers. A two-compartment population pharmacokinetic model was developed with data for 42 healthy volunteers using an iterative two-stage Bayesian method. External validation was performed by Bayesian fitting of the model developed with data for volunteers to the data for individual MDR-TB patients (in which the fitted values of the area under the concentration-time curve from 0 to 24 h [AUC0–24, fit values] were used) using the population model developed for volunteers as a prior. A Monte Carlo simulation (n = 1,000) was used to evaluate limited sampling strategies. Additionally, the 40% T MIC with the free fraction (f 40% T MIC) of ertapenem in MDR-TB patients was estimated with the population pharmacokinetic model. The population pharmacokinetic model that was developed was shown to overestimate the area under the concentration-time curve from 0 to 24 h (AUC0–24) in MDR-TB patients by 6.8% (range, −17.2 to 30.7%). The best-performing limited sampling strategy, which had a time restriction of 0 to 6 h, was found to be sampling at 1 and 5 h (r 2 = 0.78, mean prediction error = −0.33%, root mean square error = 5.5%). Drug exposure was overestimated by a mean percentage of 4.2% (range, −15.2 to 23.6%). When a free fraction of 5% was considered and the MIC was set at 0.5 mg/liter, the minimum f 40% T MIC would have been exceeded in 9 out of 12 patients. A population pharmacokinetic model and limited sampling strategy, developed using data from healthy volunteers, were shown to be adequate to predict ertapenem exposure in MDR-TB patients.

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