Background: The circumstance of how sensitive therapeutic success is under imperfect adherence is driven by the property known as forgiveness. We have previously developed a relative forgiveness (RF) criterion [1]. The relative forgiveness criterion can also be used to quantify an RF of each patient given their own drug taking behaviour. Aim: To evaluate the […]
2015
Busulfan Target Concentration Intervention Audit and Model Evaluation
Background: Intravenous busulfan is used prior to haematopoetic stem cell transplantation. All patients undergoing this procedure in New Zealand since 2012 have been treated in Auckland. A web based target concentration intervention tool (NextDose) has been used by the clinical laboratory. Demographic, dosing and concentration details and desired target concentration or target area under the […]
Application of an in silico knockout model for gastrointestinal absorption of ketones using a systems pharmacology approach
Background: There is increasing evidence in recent years of the therapeutic benefits of induced mild ketosis in various neurological disorders. A novel means of achieving ketosis is by nutritional consumption of a ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) that hydrolyses to D-β-hydroxybutyrate (BHB).[1] The absorption of ketone monoester and BHB and its disposition appears to be complicated.[2] […]
A suggestion for determining systematic bias when measuring predictive performance
Background A common method of measuring the predictive performance of models was described by Sheiner and Beal in 1981. They suggested measuring predictive performance by expressing bias and imprecision of the model by calculating the mean prediction error (MPE) and the root mean squared error (RMSE). There are occasions where the 95% confidence interval of […]
Population modelling of influenza viral kinetics, immune response, symptom dynamics and the effect of oseltamivir
Background: Oseltamivir is an oral prodrug indicated for the treatment and prophylaxis of influenza. However, there is a paucity of disease models that incorporate the time course of influenza infection with antiviral effects and host system dynamics. This information is critical to optimise dose selection and duration of treatment. Objectives: To develop an influenza disease […]
The hazards of acquiring Aspergillus positive culture in children with cystic fibrosis
Background: Lung disease is a major cause of morbidity and mortality in patients with cystic fibrosis (CF). Impaired mucociliary clearance and host defence mechanisms in the airway lead to airway infections. From very young age, children with CF suffer infections with Pseudomonas aeruginosa (P. aeruginosa) and eradication therapy with antibiotic therapy is now standard care […]
The effects of polypharmacy and Drug Burden Index on transitions in cognitive function and death: the CHAMP study
Background: Cognitive impairment is a disabling condition and is associated with mortality. Multiple medication use and the use of sedative and anticholinergic medications are associated with poor clinical outcomes including excess morbidity and cognitive impairment. Objective: To investigate the effects of multiple medication use and Drug Burden Index (DBI) on transitions in cognitive function and […]
Population pharmacokinetic modelling of itraconazole and hydroxyl-itraconazole for oral Lozanoc® and Sporanox® capsule formulations in healthy volunteers in fed and fasted state.
Background: Itraconazole is an orally active broad spectrum anti-fungal agent used for treatment of fungal infections. It has a complex absorption kinetics with high between- and within-individual variability in addition to food effects. Hydroxy-itraconazole is the predominant active metabolite. Lozanoc is a novel Mayne Pharma formulation of oral itraconazole with significantly greater bioavailability than the […]
Allopurinol dosing in patients with renal impairment
Background: Allopurinol is used to manage gout and works by reducing plasma urate concentrations. Daily doses recommended by the current renal dosing guidelines [1] fail to achieve the clinical target for plasma urate of <0.36 mmol/L in the majority of patients [2-4]. Aims 1. To explore factors that predict allopurinol response. 2. To determine the […]
Population modelling of lithium in paediatric patients with bipolar disorder: implications for dosing
Introduction. Bipolar I disorder (BP-I) leads to substantive psychosocial dysfunction. Lithium is well-established for treating BP-I in adults, however there is a paucity of information in paediatrics. Aims. To characterise the pharmacokinetics/pharmacodynamics (PK/PD) of lithium in paediatrics and to predict lithium concentrations and clinical effects for novel dosage regimens. Methods. Observed lithium concentrations and Young […]