Archive | Abstracts

Predicting the antimalarial effect of artesunate-mefloquine combination therapy using a mechanistic pharmacokinetic-pharmacodynamic model

Background: Malaria is a mosquito-borne infectious disease, with the most severe form caused by the parasite Plasmodium falciparum. The first-line defence against uncomplicated falciparum malaria is artemisinin-based combination therapy (ACT), involving multiple administrations of two or more antimalarial drugs. ACTs are highly effective worldwide, however, recently decreased efficacy of the ACT artesunate-mefloquine has been reported […]

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Online dose calculation tool for determining dosing regimens in the very young

Few tools are available to quickly calculate dose in neonates. A dosing calculator has been developed using age, weight and renal function. The aim of this calculator is to provide quick and accurate predictions of average steady state concentration (Csspred) and expected time course for a range of dosing regimens in neonates. The dosing calculator […]

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Optimal designs for warfarin INR monitoring

Background: Warfarin is used to treat and prevent blood clots. It is one of the most difficult drugs to dose accurately, with daily maintenance doses varying by more than tenfold between patients. Evidence from pharmacogenetic studies indicates the importance of CYP2C9 and VKORC1 polymorphisms in predicting warfarin dose variability. However, this information   is of limited value […]

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A mathematical model for the effect of malaria on arginine catabolism in endothelial cells

Background: Malaria is an infectious disease caused by protozoan parasites from the genus Plasmodium. P. falciparum infects red blood cells (RBCs) which thus adhere to the microvascular endothelium. The accumulation of infected RBCs cause the reduction of oxygen resulting in impaired perfusion and, eventually, organ damage [1]. The characteristics of severe malaria are decreased nitric […]

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Evaluation of an optimal design for examining melphalan pharmacokinetics in patients with multiple myeloma

Background: The optimal design of population pharmacokinetics allows parameter estimation with minimum variance and reduced cost by identifying (1) the minimum number of blood samples required from each subject, (2) the optimal blood sampling times and (3) the minimum number of subjects required. Aim: To evaluate the results of an optimal design experiment that was […]

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Population Pharmacokinetics of Vancomycin in Premature Malaysian Neonates: Identification of Predictors for Dosing Determination in the First Month of Life

Background: Nothing is known of the pharmacokinetics of vancomycin in premature Malaysian infants during the first month of life. Knowledge of the factors which affect the fate of vancomycin in these infants could lead to improved dosage regimens for this antibiotic. Methods: A one-compartment infusion model with first-order elimination was fitted to serum vancomycin concentration […]

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A population PK-PD model of unbound Docetaxel in patients with liver impairment and identification of potential covariates for initial dosage adjustment

Objectives: Docetaxel is a commonly used anti-cancer drug. Due to higher incidence of severe neutropenia in patients with impaired liver function it is rarely given to these patients. A PK model including covariates on clearance (BSA, AAG, LF and ERMBT) have been developed for total and unbound docetaxel in normal and liver impaired patients [1]. […]

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Optimal design of time-to-event models with an emphasis on dropouts in disease progression studies

Objectives: Population optimal design is a tool to increase efficiency in drug development [1]. However, the population models used in drug development are becoming more and more advanced as the models incorporate additional variables like, for example, Time-To-Event (TTE), discrete type outcomes, etc. This increase in model complexity makes model-based optimal design more relevant but the […]

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Design of survival studies for red blood cells

Background: The lifespan of red blood cells (RBCs) is unknown. All current labelling methods contain significant flaws including loss of label from viable RBCs or reincorporation of the label into new RBCs after death of the originally labelled cells. Previously proposed models for the lifespan of RBCs either assume a fixed lifespan for all cells […]

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Population pharmacokinetics of total and unbound melphalan in patients with multiple myeloma

Background: Melphalan, an alkylating agent, is an active chemotherapeutic agent in the treatment of multiple myeloma. High dose melphalan is used prior to autografting, but additional knowledge about the pharmacokinetics, combined with toxicity and efficacy data is needed to optimise the dose. Aims: To (1) investigate the pharmacokinetics of total and unbound plasma melphalan using a population approach […]

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