Archive | Abstracts

Covariate selection methods comparison, introducing the feature of a prior

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) […]

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A bounded integer model for rating and composite scale data

Background: The number of possible score values (N) in rating and composite scale data may span from a few to >100. When modeling such data, two main strategies are typically used for the baseline model: (i) the probability of each score is estimated, leading to an estimation of N-1 baseline parameters, or (ii) treating the […]

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Optimal design for determination of AUC with no prior pharmacokinetic knowledge

Objectives: To develop a method for choosing sample intervals that provide accurate estimates of area under the concentration-time curve (AUC) when using the log trapezoidal method. The developed method will only require single individual or mean pooled concentration data and will not require prior pharmacokinetic knowledge for the drug of interest, as in the case […]

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Mechanism-based modelling to optimise piperacillin plus tobramycin combination dosage regimens against Pseudomonas aeruginosa for patients with altered pharmacokinetics

Aims: Augmented renal clearance (ARC) in critically-ill patients can result in suboptimal drug exposures and potential treatment failure. This study aimed to design optimised combination dosage regimens of piperacillin and tobramycin against a Pseudomonas aeruginosa (Pa) clinical isolate and evaluate them in the hollow-fibre infection model (HFIM) for the pharmacokinetics of patients with ARC. Methods: […]

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Vancomycin dose optimisation in patients receiving high-flux haemodialysis

Background: Vancomycin is the most commonly prescribed intravenous (IV) antibiotic in the high-flux haemodialysis (HFHD) setting. The aim of this study was to develop a population pharmacokinetic (PK) model for vancomycin in HFHD to examine the probability of target attainment (PTA) of several dosing regimens of vancomycin to optimise dosing. Methods: Data were collected retrospectively […]

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The Relationship Between Busulphan AUC and the Incidence of Sinusoidal Obstruction Syndrome in Haematopoietic Stem Cell Transplants.

High dose busulphan (Bu) is an essential component of myeloablative regimens prior to Haematopoietic Stem Cell Transplantation (HSCT), but is subject to significant inter- and intra-individual pharmacokinetic variability, which is a challenge for accurate dosing within the therapeutic window. Furthermore, sinusoidal obstruction syndrome (SOS) remains a major toxicity of Bu overexposure despite the addition of […]

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A Regression Approach to Visual Predictive Checks for Population Pharmacokinetic and Pharmacodynamic Models

Objectives: To demonstrate how regression techniques can be used to perform visual predictive checks (VPCs) and prediction-corrected VPCs (pcVPCs) for population pharmacokinetic (PK) and pharmacodynamic (PD) models.  This approach negates the need for specification of intervals, or “bins”, of the independent variable. Methods: VPCs were derived using additive quantile regression (AQR). pcVPCs were generated by […]

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Population pharmacokinetics of gentamicin in paediatrics: quantifying covariate-parameter relationship using the full random effects modelling (FREM) approach

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 […]

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Assessing the completeness of a QSP model for azathioprine metabolism

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 […]

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Development of a model to predict lean liver volume (LLV) for use in scaling drug clearance

Introduction: Clearance (CL) is the most important parameter to describe the relationship between dose and exposure for drugs dosed chronically. CL, for hepatically-cleared drugs, is known to correlate with liver size [1]. Theoretically, lean liver volume (LLV), the liver volume that excludes all fat, represents the size of the metabolically active part and may scale […]

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