Background: Dual therapy of ribavirin and pegalated interferon is the first line therapy for Hepatitis C. Ribavirin has a narrow therapeutic index with high plasma concentrations resulting in haemolytic anaemia. The aim of ribavirin therapy is to reduce serum viral load whilst minimizing side effects. Strategies such as dosing on body weight or according to […]
2013
Mechanism-based modelling and sequential dosing to elucidate subpopulation synergy for antibiotic combinations
Background: Rational and prospective approaches to optimize antibiotic combination therapy are scarce. Due to the emerging global healthcare crisis caused by multidrug-resistant bacteria, more efficient and quantitative approaches to optimize combination therapy are urgently required. Nisin, a peptide antibiotic affecting pore formation in bacterial membranes and preventing peptidoglycan synthesis, is rapidly bactericidal against multiple-resistant Staphylococcus […]
Modeling of glucose absorption
Objective: The ingestion of glucose is an extensively studies process. However, few publications describe this process using a population approach and none have investigated this process over a wider range of glucose doses including knowledge of physiology. Therefore, the objective of this work was to develop a semi-mechanistic population model describing intestinal absorption of different […]
Identification of continuous covariate relationships
Objective: The objective of this presentation was to demonstrate a new method to identify continuous covariates. The investigation of time after kidney transplant as a covariate on tacrolimus bioavailability was used as an example. Methods: A total of 3100 tacrolimus concentration-time points were obtained from 242 patients who underwent kidney transplantation at Oslo University Hospital […]
A Review of Population Pharmacokinetic and Pharmacodynamic Studies of Mycophenolate in Autoimmune Disease Patients
Introduction: Mycophenolic acid (MPA), the active drug moiety of mycophenolate, is a potent immunosuppressant agent, which is increasingly being used in the treatment of patients with various autoimmune diseases. Despite the accumulation of promising clinical data on the benefits of mycophenolate in autoimmune diseases, there is a relative lack of data on its pharmacokinetics and […]
Population pharmacokinetics of vancomycin in orthopaedic patients
Aim: The objective of this study was to evaluate the pharmacokinetic properties of vancomycin in orthopaedic patients during routine clinical care using a non-linear mixed effects modelling approach. Methods: A two-compartment infusion model with first-order elimination was fitted to serum vancomycin concentration data (n = 1198 points) obtained retrospectively from routine therapeutic drug monitoring records […]
Identifiability of Population Pharmacokinetic-Pharmacodynamic Models
Background: Mathematical models are routinely used in clinical pharmacology to study the time course of concentration and effect of a drug in the body. Identifiability of these models is an essential prerequisite for the success of these studies.1 Identifiability is classified into two types, structural identifiability related to the structure of the mathematical model and […]
Relating intracellular methotrexate polyglutamate concentrations in red blood cells with clinical response in rheumatoid arthritis
Background: Methotrexate (MTX) is used as the gold standard treatment of rheumatoid arthritis (RA). However, the required dose of MTX to achieve the desired clinical outcome varies widely between individuals and is difficult to predict. MTX plasma concentrations have not proven useful as a predictor for MTX treatment outcomes in RA [1]. It has been […]
Comparison of the probability of target attainment (PTA) of anidulafungin for antifungal prophylaxis against Candida species
Background: Intermittent dosing of anidulafungin is an attractive option for antifungal prophylaxis in patients with acute lymphoblastic leukaemia (ALL) due to anidulafungin’s long half-life and concentration-dependent killing [1]. At present there is a lack of information on the likely PK-PD outcomes of anidulafungin in ALL patients. This study evaluated the probability of target attainment (PTA) […]
Evaluation of methods to handle nuisance covariates that are non-ignorable
Background: As the frequency of the covariate in the population tends to zero, alpha error inflates. Low frequencies may occur with some genotypes and concomitant medications. Since, (1) the presence of an effect cannot be determined accurately then these “rare” covariates are a nuisance, and (2) if rare covariates influence parameter estimates they are “non-ignorable”. […]