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 […]
Tag Archives | 2012
Pharmacokinetics of high-dose methotrexate in children with cancer: A mechanism-based evaluation of clearance prediction
January 27, 2012
Authors Sarapee Hirankarn (1), Nick Holford (2), Erin Dombrowsky (1), Dimple Patel (1), Jeffrey S. Barrett (1)
Affiliations 1. The Children's Hospital of Philadelphia, USA , 2. University of Auckland, New Zealand
Presentation type Oral
Presenters Sarapee Hirankarn
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 […]
A clinical trial incident: Why simple PK is sometimes not so simple
January 26, 2012
Authors Areej Turkistani (1), Sam Holford (1), Nick Holford (1)
Affiliations University of Auckland, New Zealand
Presentation type Oral
Presenters Areej Turkistani
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
January 25, 2012
Authors Troels K Bergmann (1), Stefanie Hennig (1), Katherine A Barraclough (2), Christine E Staatz (1)
Affiliations (1) University of Queensland, School of Pharmacy, Brisbane, Australia, (2) Princess Alexandra Hospital, Department of Nephrology, Brisbane, Australia
Presentation type Poster
Presenters Troels K Bergmann
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?
January 18, 2012
Authors Nick Holford (1), Sarapee Hirankarn (2), Erin Dombrowsky (2), Dimple Patel (2), Jeffrey S. Barrett (2)
Affiliations 1. University of Auckland, New Zealand, 2. Childrens Hospital of Philadelphia, USA
Presentation type Oral
Presenters Nick Holford
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
January 18, 2012
Authors Sam Holford (1), Areej Turkistani (1), Hima Madhavaram (2), Nick Holford (1)
Affiliations 1. University of Auckland, New Zealand, 2. LabPlus, Auckland, New Zealand
Presentation type Oral
Presenters Nick Holford
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 […]
A model for fat free mass in humans from very premature neonates to young adults
January 18, 2012
Authors Anita Sumpter (1), Nick Holford (2)
Affiliations 1. Starship Hospital, Auckland, New Zealand, 2. University of Auckland, New Zealand
Presentation type Oral
Presenters anita sumpter
Objectives: To describe the maturation of fat free mass (FFM) from prematurity to adulthood as a function of postmenstrual age (PMA) using nonlinear mixed effect modeling. Background: A model for FFM for adults has been well described, with different formulae for males and females (1). An extension to this model using data from age 3 […]
The pharmacokinetic profile of intravenous paracetamol in adult patients undergoing major abdominal surgery: A population analysis
January 17, 2012
Authors Katie Owens, Natalie Medlicott, Philip Murphy, Julia Kennedy, Mathew Zacharias, Sree Chary, Neil Curran, Mark Thompson-Fawcett, David Reith
Affiliations School of Pharmacy, University of Otago, University College Cork, Ireland, Dunedin Hospital, Dunedin School of Medicine, University of Otago
Presentation type Oral
Presenters Katie Owens
The aim of the present study was to determine the effect of major surgery on paracetamol glucuronidation and sulfation. 53 patients were given doses of either 1, 1.5 or 2 g of paracetamol by intravenous (IV) infusion. A combination of rich and sparse plasma and urine samples were collected over a 7 day period (Day […]
Adaptive PD-optimal design of a pilot study for a clotting time test for enoxaparin
January 16, 2012
Authors Abhishek Gulati (1), James M Faed (2), Geoffrey K Isbister (3,4), Stephen B Duffull (1)
Affiliations School of Pharmacy, University of Otago, Dunedin, New Zealand, Department of Pathology, School of Medicine, University of Otago, Dunedin, New Zealand, Department of Clinical Toxicology and Pharmacology, Calvary Mater Hospital, NSW, Australia, Discipline of Clinical Pharmacology, University of Newcastle, NSW, Australia
Presentation type Oral
Presenters Abhishek Gulati
Background: Dosing of enoxaparin, like other anticoagulants, may result in bleeding following excessive doses and clot formation if the dose is too low. There is no standard measure of enoxaparin clinical effectiveness. We recently showed that a Xa clotting time test could potentially assess the effect of enoxaparin on the clotting system [1]. Preliminary in […]
Evaluation of a Bayesian dose-individualisation method for enoxaparin
January 16, 2012
Authors Hesham S Al-Sallami (1), Michael Barras (2), Stephen B Duffull (1)
Affiliations (1) School of Pharmacy, University of Otago, Dunedin, New Zealand, (2) Royal Brisbane & Women's Hospital, Brisbane, Australia
Presentation type Oral
Presenters Hesham Al-Sallami
Background: Enoxaparin is a low molecular weight heparin used in the treatment of thrombosis. The current approved treatment dose of enoxaparin is based on total body weight and its dosing frequency is based dichotomously on creatinine clearance. Recent evidence has shown these dosing strategies to be suboptimal and Bayesian dose-individualisation has been proposed as a […]