Aim: The aim of this study was to develop a population PK model for propofol in adults that could be used to determine optimal sampling times for a prospective pharmacokinetic study. Methods: Data from 15 pharmacokinetic studies of propofol in adults were obtained from the OpenTCI Initiative [1]. A total of 7711 concentrations from 405 […]
2009
Novel diagnostics for assessing fit of logistic regression models
Background: Assessment of goodness of fit of a model to the data set is essential to ensure the model provides a reasonable description of the events seen. For logistic regression the most common diagnostic used for this purpose is binning the data and comparing the empirical probability of an event in each bin to the model […]
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. […]
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 […]
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 […]
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 […]
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) […]
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, […]
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 […]