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 […]
Tag Archives | 2011
Population Pharmacokinetics of Paracetamol in Overdose in a Single Patient
January 29, 2011
Authors Iedema JM (1), Isbister GK (2), Pillans P (1)
Affiliations (1) Princess Alexandra Hospital, Woolloongabba, Brisbane, Australia, (2) Calvary Mater Hospital, Newcastle, Australia
Presentation type Oral
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 […]
Optimal designs for population pharmacokinetic studies of the partner drugs administered with artemisinin derivatives
January 28, 2011
Authors Kris M Jamsen (1), Stephen B Duffull (2), Joel Tarning (3,4), Niklas Lindegardh (3,4), Nicholas J White (3,4), Julie A Simpson (1)
Affiliations (1) Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Melbourne, Australia, (2) School of Pharmacy, The University of Otago, Dunedin, New Zealand, (3) Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand, (4) Centre for Tropical Medicine, Churchill Hospital, Oxford, UK
Presentation type Oral
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), […]
Methods to Determine Optimal Sampling Windows for Nonlinear Mixed Effects Models
January 28, 2011
Authors Lee Kien Foo (1), James McGree (2), Stephen Duffull (1)
Affiliations (1) University of Otago, (2) Queensland University of Technology
Presentation type Oral
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 […]
Predicting Weight Using Postmenstrual Age
January 28, 2011
Authors Anita L Sumpter (1), Nick Holford (2)
Affiliations (1) Department of Anaesthesiology, University of Auckland School of Medicine, Auckland, New Zealand, (2) Department of Pharmacology and Clinical Pharmacology, University of Auckland School of Medicine, Auckland, New Zealand
Presentation type Oral
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 […]
What is needed for a dosing calculator?
January 28, 2011
Authors Brian Anderson (1), Carissa Herbert (2), Nick Holford (3), Sam Holford (4)
Affiliations (1) Department of Anaesthesiology, (2) School of Medicine, (3) Department of Pharmacology and Clinical Pharmacology; University of Auckland, Auckland, New Zealand
Presentation type Oral
Presenters Sam Holford
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 […]
The use of PKPD simulations to inform the rational use of medicines in clinical practice: the case of simvastatin circadian dosing
January 28, 2011
Authors Daniel F. B. Wright, Venkata V. Pavan Kumar, Hesham S. Al-Sallami, Stephen B. Duffull
Affiliations School of Pharmacy, University of Otago, PO Box 56, Dunedin, New Zealand
Presentation type Oral
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 : A tool for NONMEM users
January 28, 2011
Authors Eun-Kyung Lee, Gyujeong Noh
Affiliations Ewha Womans University
Presentation type Poster
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.
Quantifying Disease Progress with Inactive Treatments in Multiple Parkinson
January 28, 2011
Authors Shu Chin Ma, Nick Holford
Affiliations Department of Pharmacology and Clinical Pharmacology, University of Auckland, Auckland, New Zealand
Presentation type Poster
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 […]
Development of fluconazole dosage guidelines in critically ill patients receiving continuous venovenous hemodiafiltration
January 28, 2011
Authors Kashyap Patel (1), Jason A. Roberts (2), Jeffrey Lipman (2), Susan E. Tett (1), Megan E. Deldot (2), Carl M. Kirkpatrick (1)
Affiliations (1) The School of Pharmacy, The University of Queensland, Pharmacy Australia Centre of Excellence, Brisbane, Queensland, Australia, (2) Department of Intensive Care, Royal Brisbane and Women
Presentation type Oral
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: […]