2014

Evaluation of NONMEM 7.3.0 and Monolix 4.2.2 by Parametric Bootstrap Nick Holford, University of Auckland NONMEM 7.3.0 and Monolix 4.2.2 were evaluated in terms of parameter estimation bias and uncertainty coverage bias using a parametric bootstrap procedure. All calculations were performed using the NeSI PAN cluster. Four problems of increasing difficulty were tested: warfarin pharmacokinetics, […]

Background: Coagulation is an important process in haemostasis. It involves a complex interaction of clotting enzymes and proteins and includes numerous feedback and feedforward reactions. Warfarin, a widely used anticoagulant, has a complex dose-response relationship in addition to large between subject variability. Recently, a simulation software (CoaguSim) was developed in-house to simulate the time course […]

Introduction. For students studying pharmacy, there is a leap between class room learning and dealing with real patients in a dynamic clinical environment. We propose to bridge this gap through a game based, role-playing, software tool in which the student takes the role of a clinical pharmacist in a simulated hospital environment which allows interaction […]

Introduction. Genetic differences in warfarin metabolism (via CYP2C9) and vitamin K recycling (VKORC1) have been found to significantly influence warfarin maintenance dose requirements. A Bayesian forecasting method for warfarin therapy should predict dosing requirements without prior genetic data. Aims. The aim of this study was to determine the influence of CYP2C9 and VKORC1 genotype on […]

Background & Objectives: Efficacy benchmarking is an important decision making component during clinical drug development and comparative effectiveness in many countries would ultimately determine ranking and pricing among alternative treatments. In chronic obstructive pulmonary disease (COPD), the forced expiratory volume in 1 second (FEV1) is used to assess lung function [1], and serves as biomarker […]

Background: Paraquat poisoning is a common and serious medical problem in many parts of Asia and the Pacific. The mortality rate of this herbicide is extremely high as there is no specific and effective treatment. Aim: We analysed data collected during an ongoing cohort study on self-poisoning and from a randomized controlled trial assessing the […]

Background: Transdermal fentanyl is used to control severe pain in cancer patients. Similarly to other opioids, there is a narrow therapeutic window between pain control and toxicity and a substantial potential for side-effects. Many factors including age, gender, dose, genetic variations, kidney and liver function, and plasma protein binding, influence how opioids are processed by […]

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 […]

Background. Colistin is administered as its inactive prodrug colistin methanesulfonate (CMS) and is increasingly used as last-line therapy against multidrug-resistant Gram-negative bacteria. While pulmonary dosing of CMS is utilised in lung infections to reduce the risk of nephrotoxicity and neurotoxicity, there is a dearth of pharmacokinetic (PK) information on colistin and CMS. Quantitatively characterising the […]

Objective: Following oral administration, leflunomide is rapidly converted to its active metabolite teriflunomide via blood born metabolism and the CYP enzymes 1A2 and 2C19. Variability in enzymatic activity may contribute to the high variability in total teriflunomide concentrations (3 – 150 mg/L) achieved at standard doses. Leflunomide itself is not detectable in the plasma and […]