Despite the large utilization of vancomycin in methicillin resistant Staphylococcus aureus (MRSA) infections, there is limited information regarding the proper dosing regimen in intensive care unit patients with impaired renal function. The objective of this study was (i) to conduct a population pharmacokinetic analysis of vancomycin in a population of critically ill patients; (ii) to […]
Abstracts
Mechanism-based population modelling of dihydoartemisinin pharmacodynamics in murine malaria
Background: Murine models are powerful tools for studying erythrocytic stages of malaria infection, because parasite morphology and development are similar to that in human malaria. However, mechanism-based pharmacodynamic (PD) models for antimalarials are generally lacking, and are required to optimise dosing. Objectives: To describe the growth cycle for Plasmodium berghei and the parasitocidal effect of […]
Optimal designs for pharmacokinetic-pharmacodynamic studies of dihydroartemisinin following oral artesunate
Background: Artemisinin derivatives are the main drugs used for the treatment of uncomplicated malaria. Although these drugs remain the most powerful anti-parasitic agents available, there is now evidence for parasite resistance to artesunate, the most widely used artemisinin derivative [1]. This finding provides motivation for conducting more pharmacokinetic-pharmacodynamic (PK-PD) studies of artesunate to monitor its […]
Development and application of a pharmacokinetic model for the glycation of albumin
Background Glycated haemoglobin, HbA1c, is used commonly as a marker for glycaemic control. In patients with chronic kidney disease (CKD) red blood cells (RBCs) are removed faster from the circulation, giving less time for glycation of haemoglobin to occur [1]. Thus, HbA1c concentrations are falsely lowered in these patients. Glycated albumin (GA) has been suggested […]
Pharmacokinetics of high-dose methotrexate in children with cancer: A mechanism-based evaluation of clearance prediction
Background High-dose methotrexate (HDMTX) represents an important treatment modality in several pediatric cancers, though managing toxicities with HDMTX continues to be a challenge. Due to its narrow therapeutic window as well as significant variability in its pharmacokinetics, the current management of the MTX therapy is complicated. Urine alkalinization, vigorous hydration, and rescue with leucovorin are […]
Which matrix is the most reliable to judge the inclusion of covariates: reduction of unexplained parameter variability, increase in explained parameter variability or change in OFV?
Background: When performing a population pharmacokinetic (PK) modeling analysis covariates, such as weight, gender etc. might be included into the model to explain part of the parameter variability. Parameter variability can be defined as the sum of unexplained (random) parameter variability (UPV) and explained (predictable) parameter variability (EPV). If inclusion of a covariate on a […]
A clinical trial incident: Why simple PK is sometimes not so simple
The antibiotic dose calculator trial in children aims to find out if a web based dose calculator is better than department protocols used in 3 clinical units for achieving target concentrations of amikacin, gentamicin or vancomycin. During the trial an incident occurred when the dose calculator dose proposed a clearly inappropriate maintenance dose and dosing […]
Prediction correction: quick fix for VPC misdiagnosis in a tacrolimus popPK model
After spending weeks on modelling with little progress it occurred to us that the problem might lie with the diagnostic – not the model. Background: A VPC (visual predictive check) is a graphically representation of multiple simulations of a model. Percentiles of both the observed and the simulated data are plotted against an independent variable […]
What is the between cycle variability in methotrexate clearance?
Background High dose methotrexate (MTX) is the mainstay of treatment for many cancers. It is typically administered on repeated occasions known as ‘cycles’. Due to extensive variability in its pharmacokinetics (PK) and life-threatening toxicity, the use of repeated MTX concentration measurements to determine the duration of leucovorin dosing has decreased the incidence of severe toxicity. […]
NextDose – A web based collaborative tool for dose individualisation
A web based collaborative tool has been developed for helping with dose individualisation. It has been applied to dosing busulphan for conditioning prior to marrow transplantation. NextDose stores patient information seperately from the web interface for security. This information is stored in a non-identifiable format and requires authorised use of the NextDose application to combine […]