Tag Archives | 2015

Modeling of blood pressure lowering effect for co-administration of valsartan and amlodipine

Background: The objective of this study was to develop a pharmacodynamic (PD) model for antihypertensive effect of amlodipine and valsartan combined therapy. Methods: Pharmacokinetic (PK) modeling was first carried out for both drugs using data collected from 48 healthy volunteers receiving a combined formulation of 10mg amlodipine and 160mg valsartan as a single dose. Systolic […]

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Quantitative Assessment of Nocturia Patient’s Urination Pattern and Drug Treatment Effects using a Joint Ordered Categorical Model

Background: Nocturia occurs in about 70% of the elderly, lowering the quality of life seriously. However, due to the lack of understanding of the disease, no objective tool is available for evaluating drug effects. Objective: To develop a model for quantitative assessment of disease characteristics and drug effects in nocturia Design, Setting, and Participants: This […]

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Mechanism-based pharmacodynamic modelling approach to optimise synergistic carbapenem plus aminoglycosides combinations to combat carbapenem-resistant Acinetobacter baumannii

Introduction. Antimicrobial resistance in Gram-negative bacteria is one of the three greatest threats to human health according to the WHO, EU and other organisations. Multi-drug resistant Gram-negative bacteria commonly cause serious infections with a high rate of mortality and high degree of morbidity. In the past, β-lactams and aminoglycosides were successfully used to treat susceptible […]

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A repeated time-to-event analysis of onset and offset times of sildenafil erectile response

Objectives Sildenafil has been commonly used for the treatment of erectile dysfunction [1]. A previous research explored sildenafil’s effectiveness based on qualitative indices [2], but there has been no report on the quantitative aspect of erectile response of sildenafil. Based on this background, using a repeated time-to-event (RTTE) model, this study aimed to assess onset […]

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Pharmacokinetic modelling of enterohepatic circulation of mycophenolic acid in Malaysian lupus nephritis patients

Introduction Mycophenolic acid (MPA) is an immunosuppressant agent which is increasingly be used in treatment of lupus nephritis patients. Currently it is given as a fixed dose without drug concentration monitoring, however it is likely patients would benefit from more individualised treatment. The objective of this current study is to develop a population pharmacokinetic model […]

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Automated proper lumping for the simplification of linear systems

Background Complex system models may need to be simplified into simpler structures for many practical applications. Proper lumping is a simplification method that merges the original states into fewer pseudo states to produce a reduced system [1]. Recently a proper lumping technique has been used for the simplification of a large-scale systems pharmacological model [2]. […]

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Impact of high-flux haemodialysis on the probability of target attainment for amoxycillin/clavulanic acid combination therapy

Introduction: High-flux dialysers are widely used in patients receiving haemodialysis due to increased permeability, solute flow and positive outcomes for patients. The clearances of small molecules, including amoxycillin (Amox)/clavulanic acid (Clav), are likely to increase during high-flux haemodialysis (HFHD). This will result in lower exposure and importantly, reduced efficacy. Objectives: This simulation study evaluates the […]

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A Systematic Evaluation of Single Metrics in Discriminating Changes in Rheumatoid Arthritis Disease Activity

Background: The treat-to-target approach in the management of rheumatoid arthritis involves frequent assessments of a patient’s disease activity to guide drug dose and regimen adjustments until a pre-defined low disease activity state and/or remission has been achieved. However, which metric (single or a composite) that best reflects response to therapy and a change in disease […]

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A population PKPD model for neutropenia during Hyper-CVAD chemotherapy in non-Hodgkin lymphoma

Background: Semi-mechanistic PKPD models [1] have been previously used to describe the time-course of granulopoiesis and resulting neutropenia from cytotoxic cancer chemotherapy. The B cycle of Hyper-CVAD comprises of intravenously administered high-dose methotrexate (MTX) followed by short sequential infusions of cytarabine for treatment of aggressive non-Hodgkin lymphoma (NHL) for up to four cycles [2]. Neutropenia […]

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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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