Tag Archives | Nick Holford Prize

Mechanism-based PK/PD modelling approach to optimise combination dosage regimens against multidrug-resistant clinical isolates of Pseudomonas aeruginosa and in-vivo evaluation in a murine thigh infection model

Aims: Pseudomonas aeruginosa (Pa) is an opportunistic Gram-negative pathogen that is prevalent in bloodstream, wound and respiratory infections and has a high propensity to become multidrug-resistant. Our primary aim was to systematically evaluate synergistic killing and suppression of resistance of Pa by combinations of carbapenem plus aminoglycoside (AGS) antibiotics. Secondly, we sought to propose optimised […]

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Time-to-event model of leflunomide cessation due to toxicity in rheumatoid arthritis patients: Genetic polymorphism of CYP1A2 but not total or free teriflunomide concentrations is associated with cessation.

Aim(s) Leflunomide is used in the treatment of rheumatoid arthritis (RA), yet approximately 20 to 40% of patients cease due to toxicity. The aim was to develop a time-to-event model describing leflunomide cessation due to toxicity within a clinical cohort, and to investigate potential predictors of cessation such as total and free teriflunomide exposure and […]

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Development of a criterion to quantify forgiveness

Background: A variety of patterns of imperfect adherence have been reported including deviations in timing of doses as well as non-consecutive missed doses and drug holidays [1]. Forgiveness is a drug specific property that arises from the relationship of the duration of action and the dose interval of the drug. When the duration of action […]

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Weight-HbA1c-Insulin-Glucose (WHIG) Model for long term disease progression of Type 2 Diabetes

Background: A previously developed semi-mechanistic model [1] linked fasting serum insulin (FSI), fasting plasma glucose (FPG), and glycosylated haemoglobin (HbA1c) to characterise the disease progression of newly diagnosed type 2 diabetic (T2DM) patients. To build upon the model, weight change (DWT) as an effector to the FSI-FPG-HbA1c relationship was implemented in the present study. Methods: […]

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A reduction in between subject variability is not mandatory when adding a new covariate

Background: Population pharmacokinetic-pharmacodynamic (PKPD) analysis involves nonlinear hierarchical modelling where the mean response in a population and the variability in response from different sources are studied. It consists of two model hierarchies: a model for residual error and a model for heterogeneity termed between subject variance (BSV). The overall variability in a parameter within a […]

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Identification and initial evaluation of a prototype clotting time test for enoxaparin

Background: Enoxaparin is a low molecular weight heparin anticoagulant and is widely used in thromboprophylaxis for both prevention of primary thrombosis and at higher doses for treatment in patients with pulmonary embolism, deep vein thrombosis and acute coronary syndromes. Dosing of enoxaparin, like other anticoagulants, may result in bleeding following excessive doses and clot formation if […]

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