Introduction: Since renal dialysis machines were introduced into clinical practice in the 1950s, dialysis has immensely evolved to become the core treatment for patients with end stage renal disease. However, quantifying dialysis performance and its effect on medication clearance is still challenging. The Michaels equations, often used to calculate blood dialysance, were derived for 3 different […]
Tag Archives | PAGANZ ISOP Student Prize for Pharmacometrics
A reduced mathematical model to explore Gi/Gs preferences of the CB1 receptor
January 1, 2022
Authors Liang Yang (1), David B. Finlay (2), Xiao Zhu (3), Hayley Green(2), Michelle Glass (2), Stephen B. Duffull (1)
Affiliations (1) Otago Pharmacometrics Group, School of Pharmacy, University of Otago, Dunedin, New Zealand (2) Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand (3) Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University, Shanghai, China
Presentation type Oral
Presenters Liang Yang
Introduction: The cannabinoid type 1 receptor (CB1) induces both Gi and Gs (G-protein) pathways. The Gi pathway inhibits cyclic adenosine monophosphate (cAMP) production and Gs stimulates cAMP responses, the net cAMP response is therefore a mixture of the effects of the two pathways. CB1 shows a preference for the Gi protein and produces a net […]
Improved predictive performance using a model averaging algorithm in model-informed precision dosing of vancomycin
January 10, 2021
Authors David W. Uster (1), Sophie L. Stocker (2,3), Jane E. Carland (2,3), Richard O. Day (2,3,4), Sebastian G. Wicha (1)
Affiliations (1) Dept. of Clinical Pharmacy, Institute of Pharmacy, University of Hamburg, Hamburg, Germany (2) Dept. of Clinical Pharmacology & Toxicology, St Vincent’s Hospital, Sydney, Australia (3) St Vincent's Clinical School, University of New South Wales, Sydney, Australia (4) School of Medical Sciences, University of New South Wales, Sydney, Australia
Presentation type Oral
Presenters David W. Uster
Background: Currently, the recommendation for therapeutic drug monitoring (TDM) of vancomycin is shifting towards AUC-guided dosing through model-based precision dosing (MIPD). However, selecting the correct model is crucial to give appropriate dose recommendations (Broeker et al. CMI, 2019). The aim of the present study was to derive and evaluate a model averaging algorithm (MAA), which […]
Evaluation of the fingerprint profiles of the cannabinoid-1 receptor signalling via a kinetic modelling approach
January 6, 2019
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. Department of Pharmacology and Toxicology, University of Otago, Dunedin, NZ
Presentation type Oral
Presenters Xiao Zhu
Introduction: Biased agonism (aka ligand bias) is a term that is used to describe the ability of ligands to differentially regulate multiple signalling pathways when coupled to a single receptor. Quantification of ligand bias is critical to lead compound optimisation. Signalling is affected by rapid ligand-mediated receptor internalisation. Hence, the conventional use of equilibrium models is […]
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 […]
Internal Deterministic Identifiability of PK and PKPD Models
February 8, 2017
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: Identifiability analysis is an important aspect of the PKPD modelling framework and is divided into structural and deterministic identifiability. Structural identifiability (SI) relates to the uniqueness of outputs to parameters and inputs. Deterministic identifiability (DI) relates to the precision of parameter estimates. Here we introduce two subcategories of DI: (1) external deterministic identifiability (EDI) […]
Simplification of a pharmacokinetic model for red blood cell methotrexate disposition
January 24, 2014
Authors Shan Pan (1), Julia Korell (2), Lisa Stamp (3), Stephen Duffull (1)
Affiliations 1. School of Pharmacy, University of Otago, Dunedin, New Zealand. 2. Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden. 3. Department of Medicine, University of Otago, Christchurch, New Zealand.
Presentation type Oral
Presenters Shan Pan
Background: Methotrexate (MTX, MTXGlu1) is the gold standard treatment of rheumatoid arthritis. The time course of clinical outcomes is difficult to predict after commencing oral or subcutaneous MTX treatment. A 9-compartment pharmacokinetic (PK) model is available for describing the time course of the concentrations of MTXGlu1 and its polyglutamated metabolites (MTXGlu2-5) in red blood cells […]
Identification of continuous covariate relationships
February 4, 2013
Authors Elisabet Størset (1), Christine Staatz (2), Stefanie Hennig (2), Troels. K Bergmann (3), Nick Holford (4)
Affiliations 1. School of Pharmacy, University of Oslo, Norway, 2. School of Pharmacy, University of Queensland, Brisbane; Australian Centre of Pharmacometrics 3. Department of Pharmacology, Aarhus University, Aarhus, Denmark 4. Department of Pharmacology and Clinical Pharmacology, University of Auckland, New Zealand
Presentation type Oral
Presenters Elisabet Størset
Objective: The objective of this presentation was to demonstrate a new method to identify continuous covariates. The investigation of time after kidney transplant as a covariate on tacrolimus bioavailability was used as an example. Methods: A total of 3100 tacrolimus concentration-time points were obtained from 242 patients who underwent kidney transplantation at Oslo University Hospital […]