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 […]
2013
Development of a simplified mathematical model of the human physiome – An application relating to the cardiovascular system
Background & Objective: The overarching aim of this work is to develop a mathematical model of the human physiome as the basis of an electronic teaching tool for clinical pharmacology. The model is intended to simulate physiological functions and the effect of pathological conditions as well as pharmacological interventions over a time course of up […]
Investigations of the representation of covariate changes in NONMEM
Aims: A widely exploited feature of the mixed effect modelling software NONMEM (Icon, Ireland) is the ability to model the influence of covariates that change with time within a subject. It is documented that NONMEM represents the covariate value between TIME1 and TIME2 as the value at COV2 rather than the more intuitive value of […]
Using a Bayesian Modelling Approach with Balanced Informative Prior to Develop a Optimal Paediatric Dosing Paradigm using Scarce PK Data
Background: The conventional approaches to analyse scarce paediatric PK data with rich adult data often result in the estimated central tendency of the paediatric PK parameters being over-influenced by the adult data. Aims: The purpose of this study is to develop a Bayesian modelling approach with balancing informative prior to adequately analyse the limited PK […]
Population pharmacokinetic modelling of fentanyl for pain management in cancer patients
Background: Pain is a frequent complication of advanced cancer. Opioids are used to control severe pain. Unfortunately, they have a number of side-effects with little difference between the dose that will control pain and that which will cause toxicity. A range of factors such as age/sex/dose/delivery system/genetic variations/kidney and liver function influence how opioids are […]
Busulfan pharmacokinetics in neonates, infants, children and adults
Purpose: We have developed a pharmacokinetic model of intravenous (IV) busulfan that is applicable from neonates to adults that accounts for differences in size, body composition and age. Experimental design: Routinely collected busulfan concentration profiles were obtained at a national center for measuring busulfan concentrations. Dosing and demographic data was matched with 12,380 concentrations in […]