Archive | Abstracts

A model for procalcitonin concentrations following birth in non infected preterm neonates

January 25, 2021

Authors Jacqueline A Hannam1,2, Brian J Anderson2, Nick HG Holford1
Affiliations 1Department of Pharmacology & Clinical Pharmacology, University of Auckland; 2 Department of Anaesthesiology, University of Auckland.
Presentation type Oral
Presenters Jacqui Hannam

Attachments

Background: Procalcitonin (PCT) may be used to monitor infection and guide antibiotic therapy (1). However its usefulness in neonates is hampered due to changes following birth and events such as surgery. Methods: PCT concentrations measured in 282 non-infected pre-term and term neonates (22 and 41 weeks gestation) were provided for analysis (2). A turnover model was […]

PBPK Modeling of Vismodegib: Deconvoluting the Impact of Saturable Plasma Protein Binding, pH-dependent Solubility and Nonsink Permeation

January 23, 2021

Authors Michael J Dolton1, Po-Chang Chiang2, Fang Ma3, Jin Y Jin4, Yuan Chen3
Affiliations 1 Roche Products Australia, Level 8/30-34 Hickson Road, Millers Point NSW 2000 Australia. 2 Small Molecule Pharmaceutical Sciences, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080 USA. 3 Drug Metabolism and Pharmacokinetics, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080 USA. 4 Clinical Pharmacology, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080 USA.
Presentation type Oral
Presenters Michael Dolton

Introduction: Vismodegib displays unique pharmacokinetic characteristics including saturable plasma protein binding to alpha-1 acid glycoprotein (AAG) and apparent time-dependent bioavailability leading to non-linear PK with dose and time, significantly faster time to steady-state and lower than predicted accumulation. Objectives: Given these unique characteristics, a PBPK model was developed to explore mechanistic insights into saturable protein […]

Matters close to the heart: adaptation of tacrolimus models to inform therapeutic drug monitoring using the PRIOR approach

January 20, 2021

Authors Ranita Kirubakaran (1,2), David W. Uster (3), Stefanie Hennig (4,5), Jane E. Carland (1,2,6), Richard O. Day (1,2), Sebastian G. Wicha (3), Sophie L. Stocker (1,2,7).
Affiliations 1. St Vincent's Clinical School, The University of New South Wales, Sydney, Australia. 2. Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital Sydney, Australia. 3. Department of Clinical Pharmacy, Institute of Pharmacy, University of Hamburg, Germany. 4. Certara, Inc., Princeton, New Jersey, USA. 5. School of Clinical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Australia. 6. Department of Pharmacology, School of Medical Sciences, The University of New South Wales, Sydney, Australia. 7. School of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Australia.
Presentation type Oral
Presenters Ranita Kirubakaran

Introduction. External evaluation of published tacrolimus population pharmacokinetic models (n=17) highlighted that no available model accurately describes tacrolimus disposition in heart transplant (HTX) recipients, both with and without concomitant azole antifungal therapy.1 Concomitant azole antifungal therapy alters tacrolimus disposition substantially necessitating dose adjustments. The incorporation of azole antifungal use as a covariate may improve model-predicted […]

An ex vivo study measuring antibiotic adsorption to cardiopulmonary bypass circuitry

January 20, 2021

Authors Conor O'Hanlon (1), Nick Holford (1), Jacqueline Hannam (1), Mark Greaves (2), Brian Anderson (2)
Affiliations 1. Department of Pharmacology and Clinical Pharmacology, University of Auckland, 2. Department of Anaesthesia, Auckland City Hospital
Presentation type Poster
Presenters Conor O'Hanlon

Attachments

Background: Cephazolin and vancomycin are commonly used for antibiotic prophylaxis during surgery supported by cardiopulmonary bypass (CPB). Antibiotic pharmacokinetics (PK) can be altered by CPB through haemodilution, haemofiltration, hypothermia and drug adsorption to the circuitry (1). Adsorption can contribute to decreased antibiotic concentrations with consequent reduced prophylactic effectiveness (2). Highly protein bound drugs like cephazolin […]

Saliva for TDM of antifungal drugs: voriconazole model

January 18, 2021

Authors Hannah Yejin Kim (1,2), Anne-Grete Märtson (3), Erwin Dreesen (4), Isabel Spriet (4,5), Sebastian G Wicha (6), Andrew J McLachlan (1), Jan-Willem Alffenaar (1,2)
Affiliations 1. The University of Sydney, 2. Westmead Hospital, 3. University of Groningen, 4. KU Leuven, 5.University Hospitals Leuven, 6. University of Hamburg
Presentation type Oral
Presenters Hannah Yejin Kim

Aims. Therapeutic drug monitoring (TDM) is recommended for many antifungal drugs. Saliva sampling is a non-invasive alternative to plasma sampling. However, no clinically validated saliva models available. This study firstly aims to conduct a systematic review to evaluate the evidence supporting saliva-based TDM for azoles, echinocandins, amphotericin B, and flucytosine. The second aim is to […]

A mathematical model of CB1 receptor allosteric modulation

January 18, 2021

Authors Liang Yang (1), Xiao Zhu (1), Hayley Green(2), David B. Finlay (2), Michelle Glass (2), Stephen B. Duffull (1)
Affiliations (1) Otago Pharmacometrics Group, School of Pharmacy, University of Otago, Dunedin, New Zealand (2) Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand
Presentation type Poster
Presenters Liang Yang

Attachments

Introduction: The type 1 cannabinoid receptor (CB1) is among the most abundant G-protein coupled receptors in the central nervous system. CB1 modulates neurotransmission, and plays a vital role in both physiology and pathology. Allosteric ligands bind to a different site on the receptor to the endogenous (orthosteric) ligand and can have effects that are unique […]

Population pharmacokinetics of dimethylacetamide in children receiving intravenous busulphan

January 10, 2021

Authors Sebastian Rosser (1), Christa Nath (2), Andrew McLachlan (3), Peter Shaw (1, 2)
Affiliations 1. Children's Hosptial at Westmead Clinical School, University of Sydney, 2. Department of Oncology, The Children's Hospital at Westmead, Sydney, 3. Sydney Pharmacy School, University of Sydney
Presentation type Poster
Presenters Sebastian Rosser

Attachments

Introduction: Administration of high-dose busulphan is a critical component in many conditioning regimens for both adults and children before haemopoietic stem cell transplantation. Current intravenous formulations of busulphan contain N,N-dimethylacetamide (DMA), which is an organic solvent that acts as an excipient for drug administration. Despite available information regarding the safety of DMA use in myeloablative […]

Exploring and optimising the computational efficiency of Inductive Linearisation for estimation

January 10, 2021

Authors Sepi Sharif, Chihiro Hasegawa, Stephen B. Duffull
Affiliations School of Pharmacy, University of Otago, Dunedin, New Zealand
Presentation type Oral
Presenters Sepi Sharif

Background: Determining the optimal choice of a dose of medicine to meet the patient’s need is a complicated mathematical and statistical problem. Large between-subject variability in metabolic, excretion processes, and physiological systems involving drug effect, as well as complicated nonlinearities, are at the heart of the problem. This leads to nonlinear differential equations that need […]

Association between seropositivity and remission in rheumatoid arthritis patients receiving disease-modifying antirheumatic drugs: a retrospective analysis of 5 phase III randomized clinical trials of tocilizumab

January 10, 2021

Authors Dala N Daraghmeh(1), Ashley Hopkins(2), Catherine King(1), Ahmad Y Abuhelwa(2), Michael D Wiese(1).
Affiliations 1.School of Pharmacy and Medical Sciences, University of South Australia1, Adelaide, SA, Australia. 2College of Medicine and Public Health, Flinders University, Bedford Park 5042, SA, Australia
Presentation type Poster
Presenters Dala Daraghmeh

Attachments

Introduction. Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory disease that is often classified according to the presence of anti-cyclic citrullinated peptide antibodies (ACPA) and/or rheumatoid factor (RF) into seropositive or seronegative RA. RF and/or ACPA can be found in up to 75% of RA patients, and seropositivity may indicate higher disease activity and poorer […]

Impact of genetic and non-genetic factors on the pharmacokinetics of intravenous immunoglobulin in patients with predominantly antibody deficiencies in Malaysia

January 10, 2021

Authors Jian Lynn Lee (1), Shamin Mohd Saffian (1), Mohd Makmor-Bakry (1), Farida Islahudin (1), Hamidah Alias (2), Lokman Mohd Noh (3), Intan Hakimah Ismail (4), Noraida Mohamed Shah (1)
Affiliations 1. Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Malaysia; 2. Department of Pediatrics, UKM Medical Centre, Faculty of Medicine, Universiti Kebangsaan Malaysia, Malaysia; 3. Departments of Pediatrics, Tunku Azizah Women & Children Hospital, Malaysia; 4. Department of Pediatrics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Malaysia.
Presentation type Poster
Presenters Jian Lynn Lee

Attachments

Background: Predominantly antibody deficiency (PAD) is a rare and serious medical condition due to its likelihood to cause fatal infections. Affected patients require life-long immunoglobulin replacement therapy (IRT) and the adequacy is determined by the IgG trough at steady state in relation to clinical response. There is considerable interpatient variability in the pharmacokinetics (PK) of […]

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