Archive | Abstracts

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

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 […]

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An ex vivo study measuring antibiotic adsorption to cardiopulmonary bypass circuitry

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 […]

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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 […]

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A mathematical model of CB1 receptor allosteric modulation

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 […]

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Population pharmacokinetics of dimethylacetamide in children receiving intravenous busulphan

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 […]

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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 […]

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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

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 […]

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

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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Analysis of Laplace Approximation for Pharmaceutical Nonlinear Mixed Effects Models

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 […]

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A model-based evaluation of the effect of bosentan on bile salt disposition in sandwich-cultured human hepatocytes

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 […]

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