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 […]
2018
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 […]
Alphaxalone Anaesthesia PKPD
Background Alphaxalone is an intravenous anaesthetic that has been formulated for human use as Phaxan™, an aqueous solution of alphaxalone 10 mg mL-1 and 13% betadex. This study assessed the pharmacokinetic-pharmacodynamic (PKPD) characteristics of alphaxalone (Phaxan™) in humans. Methods: Alphaxalone 0.5 (0.42-0.55) [mean (range); mg kg-1] was given by single intravenous bolus injection of Phaxan™ to […]
An approach to evaluating mass and energy balance of pharmacokinetic systems using bond graph theory
Introduction: Quantitative systems pharmacology models are used in PKPD and pharmacometrics to describe the effects of drugs as modulators of system behaviour. In most cases the systems that are described in these models can be constructed of modular units that can be assembled en-masse to create the overall system. An example of a modular component […]
Linearisation and automatic scale reduction of bone biology QSP models for data-driven analyses
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
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
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
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
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
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 […]