Objectives: Population optimal design is a tool to increase efficiency in drug development [1]. However, the population models used in drug development are becoming more and more advanced as the models incorporate additional variables like, for example, Time-To-Event (TTE), discrete type outcomes, etc. This increase in model complexity makes model-based optimal design more relevant but the […]
Abstracts
Design of survival studies for red blood cells
Background: The lifespan of red blood cells (RBCs) is unknown. All current labelling methods contain significant flaws including loss of label from viable RBCs or reincorporation of the label into new RBCs after death of the originally labelled cells. Previously proposed models for the lifespan of RBCs either assume a fixed lifespan for all cells […]
Population pharmacokinetics of total and unbound melphalan in patients with multiple myeloma
Background: Melphalan, an alkylating agent, is an active chemotherapeutic agent in the treatment of multiple myeloma. High dose melphalan is used prior to autografting, but additional knowledge about the pharmacokinetics, combined with toxicity and efficacy data is needed to optimise the dose. Aims: To (1) investigate the pharmacokinetics of total and unbound plasma melphalan using a population approach […]
Developing a model for estimating lean body weight in children
Background: Body composition changes in relation to age and maturation. Mathematical models for estimating lean body weight (LBW) have been developed in adults. There are currently no models available to predict LBW in children as a function of age or maturation. Aim: To develop a semi-mechanistic model to estimate LBW in paediatric patients. Methods: (1)Using […]
Can PBPK Models Predict Post-Mortem Redistribution?
Background: Post-mortem redistribution (PMR) refers to changes in drug concentrations that can occur after death due to various processes such as passive diffusion from solid organs.1 Drug concentrations can also differ significantly depending on the site from which the specimen was taken.2 This can cause confusion for those trying to establish a cause of death as ‘toxic’ […]
Pharmacokinetics of Tramadol in Human Neonates, Children and Adults and in Adult Rats, Cats, Dogs, Goats and Horses
Objective: To describe human maturation and between species differences in tramadol disposition. Background: (+)-Tramadol (tramadol) and its phase I metabolite (+)-O-desmethyltramadol (M1) are weak µ-opioid receptor agonists that are structurally related to morphine. The O-demethylation of tramadol to M1, the main analgesic metabolite, is catalysed by CYP2D6. CYP2D6 polymorphisms have been shown to influence M1 production and […]
Population pharmacokinetics of oxypurinol in patients with gout receiving allopurinol
Background: Allopurinol, a pro-drug of oxypurinol, is the most common medicine used for prophylactic management of gout. The active metabolite of allopurinol, oxypurinol, is responsible for the urate lowering effect of allopurinol and is primarily renally excreted. Treatment response to allopurinol is variable in people with gout supporting the need for more information about factors which […]
Optimal designs for population pharmacokinetic studies of a drug with large assay variability for patients with restrictive sampling schedules
Objective: This work aimed to determine an optimal design for patients with restrictive sampling schedules who received a drug* that displays huge assay variability, is rapidly absorbed and has a very short elimination half-life. Methods: Rich data from 20 patients were modelled in R (using nlme) to determine the structural pharmacokinetic (PK) model, PK parameters, inter-patient and […]
Pharmacokinetics of Chloroquine in Pregnant and Non-pregnant Women in Papua New Guinea
Background: Pregnant women are one of the groups for which malaria presents a particular concern, not only for the mother but also the fetus. Treatment of symptomatic infections and the use of intermittent preventive treatment in pregnancy (IPTp) may help reduce malaria associated maternal and infant morbidity and mortality. Despite the widespread use of conventional antimalarials […]
The population pharmacokinetics of propofol: a meta-analysis of studies available from the OpenTCI Initiative
Aim: The aim of this study was to develop a population PK model for propofol in adults that could be used to determine optimal sampling times for a prospective pharmacokinetic study. Methods: Data from 15 pharmacokinetic studies of propofol in adults were obtained from the OpenTCI Initiative [1]. A total of 7711 concentrations from 405 […]