Background: Pharmacometrics aims to understand the drug-patient interaction, connects various fields such as physiology, pharmacology, pharmacotherapy, clinical pharmacy, mathematical modelling, statistics, systems biology, pharmacokinetics/-dynamics in a coherent framework to improve drug development and patient therapy outcomes. The aim of this review was to identify publications that have applied the nonlinear mixed effects (NLME) modelling approach […]
Author: Stefanie Hennig
Comparing Dosage Adjustment Methods for Once Daily Tobramycin in Children with Cystic Fibrosis
Background: Different pharmacokinetic dosage adjustment methods have been developed to individualise tobramycin treatment. This study aimed to compare several currently available methods to predict tobramycin exposure after once daily dosing in cystic fibrosis children. Methods: Retrospective data from 173 cystic fibrosis patient’s treated at the Royal Children Hospital (Brisbane) were analysed. Each patient had at […]
Concordance between criteria for covariate model building
Background: When performing a population pharmacokinetic modeling analysis covariates are often added to the model. Such additions are generally justified by improved goodness of fit and/or decreased in unexplained (random) parameter variability. Increased goodness of fit is most commonly measured by the decrease in the objective function value. Parameter variability can be defined as the […]
Which matrix is the most reliable to judge the inclusion of covariates: reduction of unexplained parameter variability, increase in explained parameter variability or change in OFV?
Background: When performing a population pharmacokinetic (PK) modeling analysis covariates, such as weight, gender etc. might be included into the model to explain part of the parameter variability. Parameter variability can be defined as the sum of unexplained (random) parameter variability (UPV) and explained (predictable) parameter variability (EPV). If inclusion of a covariate on a […]
Tobramycin in paediatric CF patients – TCI or
Aim: The aim of this study was to i) develop a population pharmacokinetic model for tobramycin in paediatric cystic fibrosis (CF) patients ii) evaluate the influence of covariates, in particular serum creatinine, and iii) test whether tobramycin in CF patients is a candidate for the use in target concentrations intervention (TCI). Methods: Retrospective demographic, dosing and concentration […]
Different ways of incorporating data below the quantification limit in datasets for parameter estimation
Background: The handling of data below the lower limit of quantification (LLOQ) and the limit of detection (LOD) continues to be a challenge in pharmacokinetic analyses. The LLOQ is the lowest concentration of an analyte in a sample which can be measured with a predefined acceptable level of accuracy and precision (± 20 %). Whereas the […]