PAGANZ ISOP Student Prize for Pharmacometrics

Introduction: Intravenous ganciclovir (IV GCV) or its oral prodrug, valganciclovir (VGCV), is used for the prevention and treatment of cytomegalovirus (CMV) infection in immunocompromised children. Studies shown a serum area under the concentration-time curve (AUC24) of ≥ 40mg·h/L is required for effective CMV prevention. Aims: To determine a population pharmacokinetic model for immunocompromised children, evaluate […]

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 […]

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 […]

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 […]

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 […]

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 […]

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) […]

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 […]

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 […]