2011

Research question: Does the dosing regimen (dose and dose interval) proposed by the dose calculator result in serum concentrations closer to the target concentration than the dose regimen achieved by currently used protocols? Background: A dosing calculator has been developed based on a pharmacokinetic analysis of vancomycin (532 subjects, 1676 concentrations), amikacin (682 subjects, 1717 […]

Background: A lack of substantial pharmacokinetic analysis in overdose exists, because of uncertainty in dose and time of ingestion, and limited sampling in the absorption phase. Population pharmacokinetic analyses with uncertainty models have been used in overdose to understand dose-concentration relationships. This study uses concentration-time data in a single patient with multiple occasions of paracetamol […]

Background: The World Health Organization recommends artemisinin-based combination therapy (ACT) as first line treatment for uncomplicated falciparum malaria1. ACT consists of a highly effective but short lived artemisinin derivative and a less effective but longer lasting partner drug(s). We have recently proposed optimal designs for future population pharmacokinetic studies of the main artemisinin derivative (Artesunate), […]

Background: D-optimality is often used to design an optimum experiment for population pharmacokinetic (PK) studies. However, obtaining samples at specific time points is not always feasible due to logistic constraints. Therefore many D-optimal designs may be executed sub-optimally and risk attaining uninformative data. Sampling windows (a time range around each of the D-optimal time points) can […]

Objectives: To describe the pattern and variability of body weight with postmenstrual age (PMA) using nonlinear mixed effect modeling (NONMEM) to create a single mathematical function that can be used from prematurity to adulthood. Background: Postmenstrual age has been shown to predict functional properties of humans such as glomerular filtration rate and drug clearance.  Widely used growth […]

Background: Once daily dosing of aminoglycosides is popular because these drugs have a concentration-dependent bactericidal spectrum and nephrotoxicity is related to a saturable uptake by the proximal renal tubules. High peak concentrations and low trough concentrations are consequently desirable. Current dosing of both aminoglycosides and glycopeptides for children in intensive care is protocol driven. Dosing in […]

Background: The overarching motivation for this research is the belief that simulations from a pharmacokinetic-pharmacodynamic (PKPD) model provide an opportunity to explore the rational use of medicines in clinical practice. The current practice of dosing simvastatin in the evening rather than the morning is presented as a motivating example. This regimen is based largely on […]

fit4NM is the software for the exploratory analysis for pharmacometrics. It helps NONMEM users check their data, fit their models using NONMEM, and evaluate their fitted models. This software is built on R and provides a user-friendly graphical interface  for the graphics and statistical analyses including running NONMEM.

Objective: To quantify the progression of Parkinson disease (PD) in patients receiving inactive control treatments in three Parkinson’s disease clinical trials. Methods: Data from 1027 patients receiving pharmacologically inactive control treatments were obtained from 3 clinical trials (DATATOP, ELLDOPA,TEMPO (1-3)) and merged using SAS (9.1). Progression was modeled using a combination of a linear function […]

Objectives: To investigate the pharmacokinetics of fluconazole in critically ill anuric patients receiving continuous venovenous hemodiafiltration (CVVHDF), and to determine a dosing regimen that achieves appropriate pharmacodynamic endpoints in this population. Design: An open-labeled study performed over a 28 month period. Setting: Intensive care unit at the Royal Brisbane and Womens’ Hospital in Australia. Patients: […]