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 […]
Archive | Abstracts
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
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
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 […]
Analysis of Laplace Approximation for Pharmaceutical Nonlinear Mixed Effects Models
January 10, 2021
Authors Mohamed Tarek (1,2), Christopher Rackauckas (1,3,4), Patrick K. Mognesen (1,5)), Vijay Ivaturi (1,4), Andreas Noack(1,5)
Affiliations 1. Pumas AI Inc., 2. University of New South Wales at Canberra, 3. Massachusetts Institute of Technology, 4. University of Maryland, 5. Julia Computing Inc.
Presentation type Poster
Presenters Mohamed Tarek
Attachments
Laplace approximation and its various approximations are some of the most commonly used techniques in pharmaceutical nonlinear mixed effects modelling to marginalise the the random effects. Classically, only Gaussian random effects have been used with transformations applied after the fact. In this work, the Laplace approximation framework is mathematically analysed showing the theoretical soundness of […]
A model-based evaluation of the effect of bosentan on bile salt disposition in sandwich-cultured human hepatocytes
January 10, 2021
Authors Pieter Van Brantegem (1), Neel Deferm (1), Marlies Oorts (1), Axelle Cooreman (2), Mathieu Vinken (2), Erwin Dreesen (3, 4), Pieter Annaert (1)
Affiliations (1) Drug Delivery and Disposition, KU Leuven, Belgium, (2) In Vitro Toxicology and Dermato-Cosmetology, VUB, Belgium, (3) Clinical Pharmacology and Pharmacotherapy, KU Leuven, Belgium, (4) Uppsala Pharmacometrics Research Group, Uppsala University, Sweden
Presentation type Oral
Presenters Pieter Van Brantegem
Attachments
Introduction Bosentan is an endothelin receptor antagonist used to treat patients with pulmonary arterial hypertension and is known to cause cholestatic liver toxicity. Bosentan is an inhibitor of the bile salt export pump (BSEP), the major efflux transporter for bile salts, but other mechanisms may also be involved. However, often high bosentan concentrations are used […]