Introduction: Procalcitonin plasma concentration (PCT) has been suggested as a biomarker for acute infection (usually bacterial). Concentrations increase rapidly within 4-6 hours of infection [1]. However PCT also increases following events such as birth and surgery without any known infection [2, 3]. It is important to understand the time course of PCT following these events […]
Tag Archives | Nick Holford Prize
Cefazolin pharmacokinetics and extent of device binding during cardiopulmonary bypass
January 21, 2022
Authors Conor J O’Hanlon (1), Jacqueline A Hannam (1), Brian J Anderson (2,3), Mark Greaves (3), Nick HG Holford (1)
Affiliations (1) Department of Pharmacology and Clinical Pharmacology, University of Auckland, Auckland, New Zealand. (2) Department of Anaesthesiology, University of Auckland, Auckland, New Zealand. (3) Department of Anaesthesia, Starship Children’s Hospital, Auckland, New Zealand.
Presentation type Oral
Presenters Conor O'Hanlon
Introduction: Cefazolin is administered routinely for antibiotic prophylaxis during cardiac surgery. However there is uncertainty in determining the correct dose due to the impact of critical illness and the cardiopulmonary bypass (CPB) machine on drug pharmacokinetics (PK). Aims: To quantify cefazolin adsorption to the CPB machine device and incorporate this into a population PK model […]
A population pharmacokinetic model of once daily intravenous busulfan in paediatrics characterising time-dependent clearance
January 10, 2021
Authors Rachael Lawson1,2, Christine E. Staatz1, Christopher J Fraser3, Stefanie Hennig4,5.
Affiliations 1 The University of Queensland, School of Pharmacy, Brisbane, QLD, Australia. 2Queensland Children’s Hospital, Pharmacy Department, Brisbane, QLD, Australia. 3Queensland Children’s Hospital, Blood and Marrow Transplant Service, Brisbane, QLD, Australia. 4School of Clinical Sciences, Queensland University of Technology, Brisbane, QLD, Australia. 5Certara, Inc., Princeton, New Jersey, USA.
Presentation type Oral
Presenters Rachael Lawson
Aims: To characterise the pharmacokinetics of busulfan in paediatrics and investigate changes in clearance over a 4-day treatment course of once daily intravenous therapy. Methods: A population pharmacokinetic model was developed using NONMEM®, based on first-order conditional estimation with interaction, in patients ≤18 years receiving once daily intravenous busulfan for haematopoietic stem cell transplant (HSCT) who had […]
External evaluation of population pharmacokinetic models of tacrolimus in adult heart transplant recipients
December 5, 2019
Authors Ranita Kirubakaran (1,2), Stefanie Hennig (3,4), Ben Maslen (5), Jane E Carland (1,2), Richard O Day (1,2), Sophie L Stocker (1,2)
Affiliations 1. St Vincent's Clinical School, UNSW, Sydney, 2. Dept of Clin Pharmacol and Toxicol, St Vincent's Hosp, Sydney, 3. School of Pharmacy, UQ, Brisbane, 4. Certara, Inc., Princeton, 5. Mark Wainwright Analytical Centre, UNSW, Sydney.
Presentation type Oral
Presenters Ranita Kirubakaran
Background. Numerous population pharmacokinetic (popPK) models of tacrolimus (TAC) in adult transplant recipients have been published. However, data on the accuracy of Bayesian forecasting with concomitant azole therapy or extrapolation to other transplant cohorts are scarce. Aims. To externally validate the predictive performances of relevant popPK models of TAC in adult heart transplant (HTX) recipients […]
The Influence of Genotype on Warfarin Dose Predictions
January 7, 2019
Authors Guangda Ma (1), Nick Holford (1), Jacqui Hannam (1), Jeff Harrison (1)
Affiliations 1. The University of Auckland
Presentation type Oral
Presenters Guangda Ma
Background & Aims: Warfarin is the most commonly prescribed oral anticoagulant worldwide, however, a narrow therapeutic range poses a barrier to safe and effective therapy. Common methods to predict warfarin dose requirements are biased at the extremes. When evaluated by simulation, Bayesian dose forecasting using a theory-based warfarin PKPD model achieves unbiased and precise dose predictions […]
Total and unbound mycophenolic acid pharmacokinetics before and after kidney transplantation
January 24, 2018
Authors David Metz (1), Nick Holford (2), Noel Cranswick (1), John Kanellis (3), Peter Trnka (4), Amanda Walker (1), Frank Ierino (1)
Affiliations 1 University of Melbourne, 2 University of Auckland, 3 Monash University, 4 University of Queensland
Presentation type Oral
Presenters David Metz
Background: An increased incidence of acute rejection is seen with underexposure to mycophenolic acid (MPA) in the initial week post kidney transplantation, particularly in high immunological risk patients (1,2). Up to 25% of individuals in contemporary drug regimens are below the proposed therapeutic range at this time (3), and these individuals cannot be identified a […]
Mechanism-based PK/PD modelling approach to optimise combination dosage regimens against multidrug-resistant clinical isolates of Pseudomonas aeruginosa and in-vivo evaluation in a murine thigh infection model
January 19, 2017
Authors Rajbharan Yadav (1), Jürgen B Bulitta (2), Jiping Wang (1), Roger L Nation (1), Cornelia B Landersdorfer (1)
Affiliations 1. Monash University, 2. University of Florida
Presentation type Oral
Presenters Rajbharan Yadav
Aims: Pseudomonas aeruginosa (Pa) is an opportunistic Gram-negative pathogen that is prevalent in bloodstream, wound and respiratory infections and has a high propensity to become multidrug-resistant. Our primary aim was to systematically evaluate synergistic killing and suppression of resistance of Pa by combinations of carbapenem plus aminoglycoside (AGS) antibiotics. Secondly, we sought to propose optimised […]
Time-to-event model of leflunomide cessation due to toxicity in rheumatoid arthritis patients: Genetic polymorphism of CYP1A2 but not total or free teriflunomide concentrations is associated with cessation.
January 7, 2015
Authors Ashley M Hopkins(1, 2), Michael D Wiese(2), Susanna M Proudman(3), Catherine E O'Doherty(2), Richard N Upton(1, 2), David JR Foster(1, 2).
Affiliations 1. Australian Centre for Pharmacometrics, 2. University of South Australia, 3. Royal Adelaide Hospital
Presentation type Oral
Presenters Ashley M Hopkins
Aim(s) Leflunomide is used in the treatment of rheumatoid arthritis (RA), yet approximately 20 to 40% of patients cease due to toxicity. The aim was to develop a time-to-event model describing leflunomide cessation due to toxicity within a clinical cohort, and to investigate potential predictors of cessation such as total and free teriflunomide exposure and […]
Development of a criterion to quantify forgiveness
January 24, 2014
Authors Piyanan Assawasuwannakit, Rhiannon Braund, Stephen B Duffull
Affiliations School of Pharmacy, University of Otago, Dunedin, New Zealand
Presentation type Oral
Presenters Piyanan Assawasuwannakit
Background: A variety of patterns of imperfect adherence have been reported including deviations in timing of doses as well as non-consecutive missed doses and drug holidays [1]. Forgiveness is a drug specific property that arises from the relationship of the duration of action and the dose interval of the drug. When the duration of action […]
Weight-HbA1c-Insulin-Glucose (WHIG) Model for long term disease progression of Type 2 Diabetes
February 4, 2013
Authors Steve Choy (1), Maria C. Kjellsson (1), Mats O. Karlsson (1), Willem de Winter (2)
Affiliations 1. Department of Pharmaceutical Biosciences, Uppsala University, Sweden. 2. Janssen Pharmaceuticals, Belgium
Presentation type Oral
Presenters Steve Choy
Background: A previously developed semi-mechanistic model [1] linked fasting serum insulin (FSI), fasting plasma glucose (FPG), and glycosylated haemoglobin (HbA1c) to characterise the disease progression of newly diagnosed type 2 diabetic (T2DM) patients. To build upon the model, weight change (DWT) as an effector to the FSI-FPG-HbA1c relationship was implemented in the present study. Methods: […]