Tenofovir (TFV) and emtricitabine (FTC), which are part of the recommended highly active antiretroviral therapy for naïve HIV patients, show a large inter-individual pharmacokinetic (PK) variability so far unexplained. We model the concentrations of plasma TFV and FTC and their intracellular metabolites (TFV-DP and FTC-TP) collected after 4 and 24 weeks of treatment in 34 […]
Archive | Abstracts
Covariate selection methods comparison, introducing the feature of a prior
January 24, 2018
Authors E. Chasseloup (1), G. Yngman (1), M.O. Karlsson (1)
Affiliations Dept of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
Presentation type Poster
Presenters M.O. Karlsson
Selecting the most externally predictive covariate of two correlated covariates can be difficult. In this study, we investigated 3 different covariate selection methods with respect to their predictive performance: a modified Stepwise Covariate Modelling (SCM), Full Fixed Effects Model (FFEM) and Prior-Adjusted Covariate Selection (PACS). The selection for SCM is agnostic (i.e. only data driven) […]
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 […]
Performance of a Theory-Based Mechanistic Model for Predicting the Target Dose of Warfarin
January 24, 2018
Authors Guangda Ma (1), Nick Holford (1)
Affiliations 1. University of Auckland
Presentation type Oral
Presenters Guangda Ma
Background: Warfarin is widely used as a treatment of venous thromboembolism and its capability to reduce the hazard of thromboembolic events has been unequivocally demonstrated. Variability between individuals, as well as a narrow therapeutic range are barriers to safe and effective warfarin therapy. Inadequate dose individualization contributes to under-utilization, 18-55% of patients who would benefit […]
Total and unbound mycophenolic acid pharmacokinetics before and after kidney transplantation
January 24, 2018
Authors David Metz (1), Nick Holford (2), Noel Cranswick (1), John Kanellis (3), Peter Trnka (4), Amanda Walker (1), Frank Ierino (1)
Affiliations 1 University of Melbourne, 2 University of Auckland, 3 Monash University, 4 University of Queensland
Presentation type Oral
Presenters David Metz
Background: An increased incidence of acute rejection is seen with underexposure to mycophenolic acid (MPA) in the initial week post kidney transplantation, particularly in high immunological risk patients (1,2). Up to 25% of individuals in contemporary drug regimens are below the proposed therapeutic range at this time (3), and these individuals cannot be identified a […]