Tag Archives | 2009

Risk of QTc Interval Prolongation and Torsades de Pointes (TdP) with Amisulpride

Background: Amisulpride has been associated with Torsades de Pointes (TdP) after overdose. But the precise relationship between amisulpride dose, QTc interval prolongation and TdP is unknown. Aim: To evaluate the dose response relationship of amisulpride for causing QTc interval prolongation and TdP. Methods: QT intervals were measured from 196 ECGs for 41 patients (23 males […]

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The Influence of Study Design on Identification of True Parameter-Covariate Relationships

Background: Utilisation of D-optimality together with clinical trial simulation are currently the primary methods used to inform clinical trial study designs and facilitate precise estimation of pharmacokinetic-pharmacodynamic (PK-PD) model parameters. A recent simulation study has extended the application of these methods to the qualitative identification of correct covariates [1]. However, the authors did not investigate the […]

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Non Linear Deconvolution

Background: Deconvolution methods using stochastic differential equations have been investigated in publications [1,2,3]. Using this method the most likely outcome of an unobservable internal process can be quantified. The (extended) Kalman Filter is used for the quantification of the internal process which is based on the observations and the model specification. Examples are often simple linear […]

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Correlation in the absorption of lamivudine and zidovudine when administered as a fixed-dose combination tablet

Background: Lamivudine (3TC) and zidovudine (AZT) are potent selective inhibitors of HIV reverse transcriptase and, due to their synergistic effect, are available as a fixed dose combination (FDC) tablet for use in antiretroviral therapy (ART). The absorption and exposure of AZT and 3TC from single component and fixed-dose combination formulations are considered to be comparable. […]

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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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