Archive | Abstracts

Population pharmacokinetics of mycophenolic acid in children and young people undergoing bone marrow and solid organ transplantation

Background: Mycophenolate mofetil (MMF) is used as an immunosuppressant for the treatment and prevention of graft-versus host disease (GVHD) in bone marrow transplantation (Nash et al 2005) and acute graft rejection in solid organ transplantation (Srinivas et al 2003). Mycophenolic acid (MPA) is the active metabolite of MMF. MPA displays variability in treatment response which supports the need for individualised […]

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Robust D-optimal Design of Nonlinear Fixed Effects Pharmacokinetic Model

Background: D-optimality is often used to design an optimum experiment for the purpose of parameter estimation. When the model is nonlinear, D-optimal designs depend on the nominal parameter values in the model, which are unknown. In order to address this dependency issue, various robust optimal design methods have been introduced [1, 2]. These methods utilize prior […]

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A case for routine monitoring of enoxaparin treatment

Background: Enoxaparin is a low molecular weight heparin (LMWH) used in the treatment of thrombosis. Unlike unfractionated heparin (UFH), no routine monitoring of plasma activity is recommended for enoxaparin treatment. The activity of enoxaparin in plasma is determined by assaying anti-activated factor X (anti-Xa). Aim: (1) To identify an anti-Xa treatment target for enoxaparin. (2) […]

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Recirculatory Modelling of Nasal Fentanyl in Man

Aim: Fentanyl is a potent opioid analgesic used for post-operative management of acute pain and breakthrough cancer pain. During the development of a nasal delivery method for fentanyl, several clinical studies were completed. These included a study of fentanyl delivery via i.v. and nasal routes with venous blood sampling and measurement of post-operative pain scores1, […]

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Pharmacokinetics of Ethanol in the Presence of Methanol

Background: In Australasia methanol overdoses are treated with high doses of ethanol. Appropriate dosing recommendations are lacking and in some cases dosing of ethanol is inadequate. There are no models for ethanol pharmacokinetics in the presence of methanol available in the literature. Aim: The overall aim is to develop dosing guidelines for ethanol treatment of […]

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Population Pharmacokinetics Of Gentamicin In Very Premature Neonates

Gentamicin in combination with benzylpenicillin, is widely used as empiric treatment in early onset neonatal sepsis. The aim of this study is to explore influence of potential covariates on the pharmacokinetic parameters of gentamicin in very premature neonates. A population pharmacokinetic model was developed using NONMEM V (version 1.1). Serum gentamicin concentrations retrospectively collected from […]

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Mechanism-based Pharmacodynamic (PD) Modeling of Phenotypic Tolerance in Pseudomonas aeruginosa for Ceftazidime

Background: Phenotypic tolerance describes the situation in which bacteria are resistant to antibiotics but are genotypically susceptible. Such tolerance may be important for optimal antibiotic therapy. Objectives: 1) To develop a mechanism-based PD model that describes the potential phenotypic tolerance of P. aeruginosa at high initial inocula (CFUo; CFU: colony forming units) to ceftazidime. 2) To propose strategies […]

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An assessment of methods for modelling regional pharmacokinetics – pooled data, pooled parameter estimates or NONMEM?

Aim: Understanding the clinical behaviour of drugs sometimes requires understanding the kinetics (and dynamics) of the drug in its target organ (e.g. the cerebral uptake of anaesthetics and analgesics). One method of studying regional (organ) kinetics is by simultaneously measuring the time-courses of the concentration of the drug in blood entering and leaving the organ. […]

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Lean body weight versus total body weight for propofol dosing

Background: Clinicians have observed longer awakening times for obese compared to normal-weight patients when propofol is dosed as per label guidelines on Total Body Weight (TBW).  This may be explained by the non-linear relationship between TBW and CL described by Schuttler et al1.  Lean Body Weight (LBW) has been reported to have a linear relationship with […]

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The evaluation of an individualised dosing strategy derived from population PK modelling and simulation

Background: Recently published enoxaparin dosing guidelines for obese and renally impaired patients are purported to increase the probability of achieving and maintaining anti-Xa (aXa) concentrations within the therapeutic range (TR) of 500-1000 IU/L. Exposure-response data indicate that concentrations greater than the TR increase the risk of bleeding, while concentrations less than the TR increase mortality. Aim: To […]

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