High dose busulphan (Bu) is an essential component of myeloablative regimens prior to Haematopoietic Stem Cell Transplantation (HSCT), but is subject to significant inter- and intra-individual pharmacokinetic variability, which is a challenge for accurate dosing within the therapeutic window. Furthermore, sinusoidal obstruction syndrome (SOS) remains a major toxicity of Bu overexposure despite the addition of […]
Archive | Abstracts
Population pharmacokinetics of gentamicin in paediatrics: quantifying covariate-parameter relationship using the full random effects modelling (FREM) approach
January 24, 2018
Authors Llanos-Paez C.C, Staatz Christine E, Hennig Stefanie.
Affiliations The University of Queensland
Presentation type Oral
Presenters Carolina Llanos-Paez
Objectives: To (i) evaluate the suitability of a previous published population pharmacokinetic (PK) model of gentamicin in paediatric oncology patients1 in predicting drug exposure in non-oncology paediatric patients and (ii) investigate the relationship between PK parameters and covariates in both oncology and non-oncology paediatric patients using the full random-effect (FREM) covariate modelling approach.2 Methods: Data […]
Assessing the completeness of a QSP model for azathioprine metabolism
January 24, 2018
Authors Vijay Kumar Siripuram (1), Daniel F B Wright (1), Murray L Barclay (2), Stephen B Duffull (1)
Affiliations (1). Otago Pharmacometrics Group, School of Pharmacy, University of Otago, Dunedin, New Zealand, (2). Departments of Gastroenterology & Clinical Pharmacology, Christchurch Hospital, New Zealand
Presentation type Oral
Presenters Vijay Kumar Siripuram
Introduction: A QSP model for azathioprine metabolism was developed from known mechanistic pathways and expert opinion. The model was intended to predict the concentrations of 6-thioguanine nucleotides (TGN) and 6-methyl mercaptopurine (MMP) under different clinical scenarios [1-3]. The model was able to predict 6-TGN and 6-MMP for typical individuals but it was unable to predict […]
Development of a model to predict lean liver volume (LLV) for use in scaling drug clearance
January 24, 2018
Authors Jaydeep Sinha (1), Stephen Duffull (1), Bruce Green (2), Hesham Al-Sallami (1)
Affiliations 1. Otago Pharmacometrics Group, School of Pharmacy, University of Otago, Dunedin, New Zealand, 2. Model Answers Pty Ltd, Brisbane, Australia
Presentation type Oral
Presenters Jaydeep Sinha
Introduction: Clearance (CL) is the most important parameter to describe the relationship between dose and exposure for drugs dosed chronically. CL, for hepatically-cleared drugs, is known to correlate with liver size [1]. Theoretically, lean liver volume (LLV), the liver volume that excludes all fat, represents the size of the metabolically active part and may scale […]
Meta-analysis of snake venom pharmacokinetics in humans
January 24, 2018
Authors Suchaya Sanhajariya (1,2), Stephen B. Duffull (2), Geoffrey K. Isbister (1)
Affiliations 1. School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia, 2. School of Pharmacy, University of Otago, Dunedin, New Zealand
Presentation type Oral
Presenters Suchaya Sanhajariya
Background: Snake envenomation can result in devastating local and systemic effects, which requires hospitalisation, and on occasion permanent disabilities and fatality in severe cases [1]. The management of snake envenomation involves supportive treatment and administration of snake specific antivenoms to neutralise free venom and prevent further envenomation. The knowledge of snake venom pharmacokinetics in humans […]
Combined population pharmacokinetic model of tenofovir and emtricitabine and their active intracellular metabolites in HIV Patients from the ANRS 134-COPHAR 3 trial
January 24, 2018
Authors Julie Bertrand (1), Aurélie Barrail-Tran (2), Rada Savic (3), Alain Pruvost (4), Anne-Marie Taburet (2), France Mentré (1), Céline Verstuyft (5) and the ANRS 134-COPHAR 3 trial group
Affiliations (1) UMR 1137 IAME INSERM Université Paris Diderot, (2) AP-HP, Hôpital Bicêtre, Pharmacie Clinique; Université Paris Sud ; INSERM UMR 1184, Center for Immunology of Viral Infections and Autoimmune Diseases, (3) Department of Bioengineering and Therapeutic Sciences, University of California San Francisco (4) Service de Pharmacologie et d’Immunoanalyse (SPI), plateforme SMArt-MS, CEA, INRA, Université Paris-Saclay, 91191, Gif sur Yvette, France, (5) Service de génétique moléculaire et pharmacogénétique, hôpital Bicêtre, AP-HP; Université Paris Sud; INSERM UMR 1184, Center for Immunology of Viral Infections and Autoimmune Diseases
Presentation type Oral
Presenters Julie Bertrand
Tenofovir (TFV) and emtricitabine (FTC), which are part of the recommended highly active antiretroviral therapy for naïve HIV patients, show a large inter-individual pharmacokinetic (PK) variability so far unexplained. We model the concentrations of plasma TFV and FTC and their intracellular metabolites (TFV-DP and FTC-TP) collected after 4 and 24 weeks of treatment in 34 […]
Covariate selection methods comparison, introducing the feature of a prior
January 24, 2018
Authors E. Chasseloup (1), G. Yngman (1), M.O. Karlsson (1)
Affiliations Dept of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
Presentation type Poster
Presenters M.O. Karlsson
Selecting the most externally predictive covariate of two correlated covariates can be difficult. In this study, we investigated 3 different covariate selection methods with respect to their predictive performance: a modified Stepwise Covariate Modelling (SCM), Full Fixed Effects Model (FFEM) and Prior-Adjusted Covariate Selection (PACS). The selection for SCM is agnostic (i.e. only data driven) […]
A bounded integer model for rating and composite scale data
January 24, 2018
Authors Mats O. Karlsson and Gustaf Wellhagen
Affiliations Dept of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
Presentation type Oral
Presenters Mats O Karlsson
Background: The number of possible score values (N) in rating and composite scale data may span from a few to >100. When modeling such data, two main strategies are typically used for the baseline model: (i) the probability of each score is estimated, leading to an estimation of N-1 baseline parameters, or (ii) treating the […]
Optimal design for determination of AUC with no prior pharmacokinetic knowledge
January 24, 2018
Authors Jim H. Hughes (1), Richard N. Upton (1), Stephanie E. Reuter (2), Mitch A. Phelps (3), David J.R. Foster(1)
Affiliations 1. Australian Centre for Pharmacometrics, School of Pharmacy and Medical Sciences, University of South Australia, 2. School of Pharmacy and Medical Sciences, University of South Australia, 3. Division of Pharmaceutics, College of Pharmacy, The Ohio State University
Presentation type Oral
Presenters Jim H. Hughes
Objectives: To develop a method for choosing sample intervals that provide accurate estimates of area under the concentration-time curve (AUC) when using the log trapezoidal method. The developed method will only require single individual or mean pooled concentration data and will not require prior pharmacokinetic knowledge for the drug of interest, as in the case […]
Mechanism-based modelling to optimise piperacillin plus tobramycin combination dosage regimens against Pseudomonas aeruginosa for patients with altered pharmacokinetics
January 24, 2018
Authors Rajbharan Yadav (1), Kate E. Rogers (1,2), Phillip J. Bergen (2), Jürgen B. Bulitta (3), Carl M. J. Kirkpatrick (2), Steven C. Wallis (4), David L. Paterson (4), Roger L. Nation (1), Jeffrey Lipman (5), Jason A. Roberts (4,5,6) and Cornelia B. Landersdorfer (1,2)
Affiliations 1. Drug Delivery, Disposition and Dynamics, 2. Centre for Medicine Use and Safety, Monash University, Parkville, VIC, Australia; 3. Center for Pharmacometrics and Systems Pharmacology, University of Florida, Orlando, FL, USA; 4. Centre for Clinical Research, 5. Royal Brisbane and Women’s Hospital, 6School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia.
Presentation type Oral
Presenters Rajbharan Yadav
Aims: Augmented renal clearance (ARC) in critically-ill patients can result in suboptimal drug exposures and potential treatment failure. This study aimed to design optimised combination dosage regimens of piperacillin and tobramycin against a Pseudomonas aeruginosa (Pa) clinical isolate and evaluate them in the hollow-fibre infection model (HFIM) for the pharmacokinetics of patients with ARC. Methods: […]