2018

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 […]

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 […]

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 […]

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 […]

Background: Snake envenomation can result in devastating local and systemic effects, which requires hospitalisation, and on occasion permanent disabilities and fatality in severe cases [1]. The management of snake envenomation involves supportive treatment and administration of snake specific antivenoms to neutralise free venom and prevent further envenomation. The knowledge of snake venom pharmacokinetics in humans […]

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 […]

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) […]

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 […]

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 […]

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: […]