Phylinda L. S. Chan

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We have modelled the Unified Parkinson’s Disease Rating Scale (UPDRS) scores collected in 800 subjects followed for 8 years. Newly diagnosed and previously untreated subjects were initially randomized to treatment with placebo, deprenyl, tocopherol or both and, when clinical disability required, received one or more dopaminergic agents (levodopa (carbidopa(More)
The purpose of the study was to describe the population pharmacokinetics of levodopa in patients with Parkinson’s disease studied in 5 trials (10 occasions) over 4 years. Twenty previously untreated Parkinsonian patients were investigated. Each trial consisted of a 2-hr IV infusion of levodopa (1 mg/kg/h) with concomitant oral carbidopa given on two(More)
AIMS To develop a population pharmacokinetic model for maraviroc, a noncompetitive CCR5 antagonist, after oral administration of tablets to healthy volunteers and asymptomatic HIV-infected subjects and to quantify the inherent variability and influence of covariates on the parameters of the model. METHODS Rich pharmacokinetic data available from 15(More)
Clinicians recognize levodopa has a short-duration response (measured in hr) and a long-duration response (measured in days) in Parkinson's disease. In addition there is a diurnal pattern of motor function with better function in the morning. Previous pharmacokinetic-pharmacodynamic modeling has quantified only the short-duration response. We have developed(More)
Using simulated viral load data for a given maraviroc monotherapy study design, the feasibility of different algorithms to perform parameter estimation for a pharmacokinetic-pharmacodynamic-viral dynamics (PKPD-VD) model was assessed. The assessed algorithms are the first-order conditional estimation method with interaction (FOCEI) implemented in NONMEM VI(More)
AIM To use non-linear mixed effects modelling and simulation techniques to predict whether PF-04878691, a toll-like receptor 7 (TLR7) agonist, would produce sufficient antiviral efficacy while maintaining an acceptable side effect profile in a 'proof of concept' (POC) study in chronic hepatitis C (HCV) patients. METHODS A population(More)
Domagrozumab, a monoclonal antibody that binds to myostatin, is being developed for Duchenne muscular dystrophy (DMD) boys following a first-in-human study in healthy adults. Literature reporting pharmacokinetic parameters of monoclonal antibodies suggested that body-weight- and body-surface-area-adjusted clearance and volume of distribution estimates(More)
• Initialisation of the R console • Exploratory graphical analysis • Parameter estimation with Monolix using SAEM and model evaluation in Xpose • Parameter estimation in NONMEM using FOCE and model evaluation in Xpose • Parameter estimation in WinBUGS using MCMC • Comparison of parameter estimates • Updating parameter estimates in the MDL Parameter Object(More)
The purpose of this analysis is to describe how levodopa pharmacokinetic and pharmacodynamic parameters change over the first 4 years of long-term levodopa treatment in patients with Parkinson’s disease. Twenty previously untreated Parkinsonian patients were admitted to the general clinical research center (GCRC) for 4 days at the beginning of long-term(More)
To externally validate the model predictions of a DATATOP cohort analysis through application of clinical trial simulation with the study design of the ELLDOPA trial. The stochastic pharmacokinetic-pharmacodynamic and disease progress model was developed from the large DATATOP cohort of patients followed for 8 years. ELLDOPA was designed to detect a(More)
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