Paracetamol and diclofenac additive effects after tonsillectomy

Background: Paracetamol combined with diclofenac is commonly used to control postoperative pain in children. Diclofenac pharmacokinetics, and paracetamol pharmacokinetics (PK) and dynamics (PD) (analgesia) have been described with these drugs used separately (1, 2). A model for the combination of paracetamol with diclofenac would be useful for improving analgesia in children. Methods: A randomised, placebo […]

Population Modelling of Vildagliptin as an Inhibitor and Substrate of Dipeptidylpeptidase IV and its Effects on Glucagon-Like Peptide 1, Glucose, and Insulin

Background. Vildagliptin acts by inhibiting dipeptidyl peptidase IV (DPP-4), thereby increases active GLP-1 (glucagon-like peptide 1) concentrations and decreases plasma glucose in diabetic patients. Objectives. To develop a mechanism-based population PK/PD model that simultaneously describes and predicts vildagliptin pharmacokinetics and its effects on DPP-4 activity and the underlying glucose-insulin-GLP-1 system. Methods. Data used for model […]

Treatment of malaria: from drug discovery to optimisation of current therapies.

  Almost 40% of the world’s population live in malaria endemic areas, with each year about a quarter of a billion people experiencing clinical malaria and an estimated 655,000 deaths. With no vaccine currently available, artemisinin-based combination therapies are the first-line defence against malaria. These therapies have been highly effective worldwide until recent reports from […]

The design of a pharmacokinetic study of Intranasal Fentanyl

Objective:  To create a sampling schedule for a population pharmacokinetic study of Intranasal Fentanyl (INF) in paediatric patients presenting to the emergency department of a tertiary care hospital. Methods:   A search of the literature was conducted to determine reasonable assumptions regarding the underlying structural model, pharmacokinetic parameters and appropriate methods for scaling down values of […]

Mechanism-based modelling of antibiotics to optimally cure patients and prevent resistance: progress, gaps, and future perspectives

Background: Substantial progress of mechanism-based and empirical modelling for anti-infectives over the past decade has enabled these models to rationally translate the time-course of killing and emergence of resistance from in vitro to animal infection models and ultimately to patients. Objectives: To illustrate applications of translational mechanism-based models for anti-infective mono- and combination therapy and […]

Assessment of vancomycin dosing regimens in Intensive Care Unit patients with impaired renal function

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 […]

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 […]