Objectives: To (i) evaluate the suitability of a previous published population pharmacokinetic (PK) model of gentamicin in paediatric oncology patients1 in predicting drug exposure in non-oncology paediatric patients and (ii) investigate the relationship between PK parameters and covariates in both oncology and non-oncology paediatric patients using the full random-effect (FREM) covariate modelling approach.2 Methods: Data […]
Tag Archives | 2018
Assessing the completeness of a QSP model for azathioprine metabolism
January 24, 2018
Authors Vijay Kumar Siripuram (1), Daniel F B Wright (1), Murray L Barclay (2), Stephen B Duffull (1)
Affiliations (1). Otago Pharmacometrics Group, School of Pharmacy, University of Otago, Dunedin, New Zealand, (2). Departments of Gastroenterology & Clinical Pharmacology, Christchurch Hospital, New Zealand
Presentation type Oral
Presenters Vijay Kumar Siripuram
Introduction: A QSP model for azathioprine metabolism was developed from known mechanistic pathways and expert opinion. The model was intended to predict the concentrations of 6-thioguanine nucleotides (TGN) and 6-methyl mercaptopurine (MMP) under different clinical scenarios [1-3]. The model was able to predict 6-TGN and 6-MMP for typical individuals but it was unable to predict […]
Alphaxalone Anaesthesia PKPD
January 24, 2018
Authors Colin Goodchild (1), Juliet Serrao (1), John Sear (2), and Brian J Anderson (3)
Affiliations 1. Drawbridge Pharmaceuticals Pty Ltd, Victoria, Australia 2. Nuffield Dept of Anaesthetics, University of Oxford, UK 3. Dept of Anaesthesiology, University of Auckland, NZ
Presentation type Oral
Presenters Brian Anderson
Background Alphaxalone is an intravenous anaesthetic that has been formulated for human use as Phaxan™, an aqueous solution of alphaxalone 10 mg mL-1 and 13% betadex. This study assessed the pharmacokinetic-pharmacodynamic (PKPD) characteristics of alphaxalone (Phaxan™) in humans. Methods: Alphaxalone 0.5 (0.42-0.55) [mean (range); mg kg-1] was given by single intravenous bolus injection of Phaxan™ to […]
An approach to evaluating mass and energy balance of pharmacokinetic systems using bond graph theory
January 24, 2018
Authors Stephen Duffull (1), Soroush Safaei (2), Peter Hunter(2)
Affiliations (1) Otago Pharmacometrics Group, School of Pharmacy, University of Otago; (2) Auckland Bioengineering Institute, University of Auckland
Presentation type Oral
Presenters Stephen Duffull
Introduction: Quantitative systems pharmacology models are used in PKPD and pharmacometrics to describe the effects of drugs as modulators of system behaviour. In most cases the systems that are described in these models can be constructed of modular units that can be assembled en-masse to create the overall system. An example of a modular component […]
Linearisation and automatic scale reduction of bone biology QSP models for data-driven analyses
January 24, 2018
Authors Chihiro Hasegawa (1, 2) and Stephen B. Duffull (1)
Affiliations 1. University of Otago, 2. Ono Pharmaceutical Co., Ltd.
Presentation type Oral
Presenters Chihiro Hasegawa
Background: Bone biology is physiologically complex. Peterson et al [1] developed a QSP model consisting of 28 states that links integrated calcium homeostasis, hormonal control mechanisms and bone remodelling which consists of two continuous processes, (i) bone resorption coordinated by osteoclasts, and (ii) bone formation by osteoblasts. While the model naturally accommodates homeostatic mechanisms it […]
Kinetic modelling of ligand mediated internalisation
January 24, 2018
Authors Xiao Zhu (1), David B Finlay (2), Michelle Glass (2), Stephen B Duffull (1)
Affiliations 1. Otago Pharmacometrics Group, School of Pharmacy, University of Otago, Dunedin, New Zealand, 2. Centre for Brain Research and Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
Presentation type Oral
Presenters Xiao Zhu
Introduction: Internalisation is by its nature kinetic. Hence, application of the standard assumption of equilibrium conditions used by pharmacologists to determine the equilibrium constant (KD) is not obvious for either the ligand-mediated internalisation pathway or other functional assays that occur over the same timeframe as internalisation. However, it is also difficult or impossible to estimate […]
Evaluation of assumptions underpinning pharmacometric models
January 24, 2018
Authors Qing Xi Ooi (1), Daniel F.B. Wright (1), Geoffrey K. Isbister (2), Stephen B. Duffull (1)
Affiliations 1. School of Pharmacy, University of Otago, Dunedin, New Zealand, 2. School of Medicine and Public Health, The University of Newcastle, Newcastle, Australia
Presentation type Oral
Presenters Qing Xi Ooi
Background: All models are underpinned by assumptions. The validity of any inference drawn from a model depends on the appropriateness and likely impact of the underlying assumptions [1]. However, in the literature surrounding quantitative pharmacology models and pharmacometrics, assumptions inherent to model development and use are not routinely acknowledged, described, or evaluated. This casts doubt […]
A population pharmacokinetic model for 51Cr EDTA to estimate renal function
January 24, 2018
Authors Isabelle H.S. Kuan (1), Stephen B. Duffull (1), Tracey L. Putt (2), John B.W. Schollum (2), Robert J. Walker (2), Daniel F.B. Wright (1)
Affiliations 1. School of Pharmacy, University of Otago, Dunedin, New Zealand, 2. Department of Medicine, University of Otago, Dunedin, New Zealand
Presentation type Oral
Presenters Isabelle H.S. Kuan
Background 51Cr EDTA is a radioisotope used to estimate glomerular filtration rate (GFR), particularly in patients receiving renally cleared anticancer agents such as carboplatin. We propose that current methods for determining 51Cr EDTA clearance from plasma radioactivity (counts/minute) result in biased estimates of GFR. The aims of the study were (i) to develop and test […]
Pharmacokinetics and metabolism of dabrafenib and trametinib in BRAF V600E/K metastatic melanoma
January 24, 2018
Authors Hannah Y Kim (1), Xiaoman Liu (1), Janna K Duong (1), Georgina V Long (2), Maria Gonzalez (2), Alexander M Menzies (2), Alan V Boddy (1)
Affiliations 1. Faculty of Pharmacy, University of Sydney, Sydney, NSW, Australia, 2. Melanoma Institute Australia and School of Medicine, University of Sydney, Sydney, NSW, Australia.
Presentation type Oral
Presenters HANNAH YEJIN KIM
Introduction. The combination of a BRAF inhibitor, dabrafenib and a MEK inhibitor, trametinib (CombiDT) has improved survival outcomes compared with chemotherapy or BRAF inhibitor monotherapy in advanced BRAF V600E/K melanoma. However, the use of CombiDT has a high incidence of pyrexia, causing treatment delays (Menzies, 2015). The pharmacokinetics and metabolism of dabrafenib and trametinib may […]
ANZDATA: Pharmacology based time to event analysis for death and renal transplant failure
January 24, 2018
Authors Nick Holford (1), David Metz (2), Amanda Walker (2), Noel Cranswick (2), Joshua Kausman (2), Susan Donath (2), Frank Ierino (2)
Affiliations 1. University of Auckland, 2. University of Melbourne
Presentation type Oral
Presenters Nick Holford
Background: The ANZDATA registry (http://www.anzdata.org.au/v1) has collected data on all patients receiving a renal transplant in Australia or New Zealand since 1977 Objective: To describe the effect of immunosuppressant medicines on time to death and time to renal transplant failure Methods: Demographic data and the daily dose of medicines used as immunosuppressants were extracted from […]