Quantifying the Dose-Response of Unfractionated Heparin Using a System Pharmacology Model of Coagulation

Introduction: Unfractionated heparin (UFH) is commonly used in the treatment and prevention of a variety of thromboembolic disorders. Its short duration of action and reversibility of its effect with the use of protamine sulphate make it the agent of choice in acute settings such as cardiac surgery. However, optimal dosing of UFH remains challenging partly due […]

A Population Pharmacokinetic Model of Phenobarbitone in Neonates to Determine Oral Bioavailability and Facilitate Individualised Dosing

Background: Phenobarbitone is the most commonly used first-line drug for the treatment of neonatal seizures. A number of previous studies, with small subject numbers, have identified covariates that may influence the pharmacokinetics of phenobarbitone but results have been inconsistent. In particular, oral bioavailability is relatively poorly described and doses are commonly reported as being the […]

PBPK modeling for lindane across different species

Interspecies differences are one of the important factors to consider when extrapolating a physiologically based pharmacokinetic (PBPK) model from one species to another. As some of the parameters used in PBPK models are not always available from in-vitro/in-vivo experiments or previous literature, it is important to know how to estimate the parameters from one species […]

Modelling of delivery kinetics of gentamicin administered through umbilical long lines

Introduction:Gentamicin is commonly used in the NICU setting and is often administered via long lines, such as umbilical venous catheters, which increases variability in the rate of administration. This variability is not taken into account when considering drug delivery in neonates and recommendations are extrapolated from adult data. We aimed to model drug delivery parameters […]

A Population Pharmacokinetic Study of Caffeine Citrate in Chinese Premature Neonates

Objective: Apnea of prematurity (AOP) is defined as an attack of apnea for at least 20 seconds, with bradycardia and cyanosis. It is a common phenomenon in the neonatal intensive care unit (NICU). Caffeine citrate, one of the methylxanthines, is used to suppress or to prevent AOP attack. This study aimed to develop a population pharmacokinetic (popPK) […]

Future work in Auckland: procalcitonin in healthy and infected neonates to inform PKPD disease progression modelling

Appropriate antimicrobial therapy in neonates and babies is complicated by pharmacokinetic (PK) changes with age, body size and disease. Additionally we lack pharmacodynamic (PD) measures to gauge patient response. A correlation exists between elevated concentrations of procalcitonin (PCT) and infection +/- sepsis butmultiple other factors also contribute to PCT fluctuations (1, 2). For example, PCT […]

Parameter Analysis for PBPK Model for Enalapril

Physiologically based pharmacokinetic (PBPK) modeling is valuable for drug development (Phase I). While PBPK models may share similar compartmental structures (e.g., blood, liver) for different species, a distinct set of physiological (e.g. compartmental volume and blood flow rate) and drug-specific (e.g. metabolism and clearance rates) parameters need to be used in different species. However, it […]

Simulations to explore studies of propofol infusions in neonates and infants

There are no validated propofol infusion regimens in neonates and infants. Existing pharmacokinetic pharmacodynamic (PKPD) models do not include data from babies under the age of 1 year (1) making dosing in this population empirical, largely based on recommendations from Steur et al (2). Steur and colleagues recommend a bolus dose between 3-5 mg·kg-1 followed by infusion rates […]

PAGANZ Workshop: CellML and OpenCOR

Over the past 10 year quantitative systems pharmacology has become an integral part of pharmacometrics.  While the models and methods used in a QSP framework are novel to pharmacometricians they have been well established in the disciplines of systems biology and bioengineering.  Software (e.g. CellML, SBML, …) for specifying models and enabling simulations from models […]

Twenty Years of PAGANZ

The PAGANZ 2019 meeting in Auckland celebrates the twentieth PAGANZ meeting held in Australasia. The original speakers at PAGANZ in 1999 who are also present at PAGANZ 2019 reflects the beneficial effect of pharmacometrics on longevity and friendship. Pharmacometrics is the boom growth field in clinical pharmacology. It has other names which serve local purposes […]