Objectives: To describe the maturation of fat free mass (FFM) from prematurity to adulthood as a function of postmenstrual age (PMA) using nonlinear mixed effect modeling. Background: A model for FFM for adults has been well described, with different formulae for males and females (1). An extension to this model using data from age 3 […]
Abstracts
The pharmacokinetic profile of intravenous paracetamol in adult patients undergoing major abdominal surgery: A population analysis
The aim of the present study was to determine the effect of major surgery on paracetamol glucuronidation and sulfation. 53 patients were given doses of either 1, 1.5 or 2 g of paracetamol by intravenous (IV) infusion. A combination of rich and sparse plasma and urine samples were collected over a 7 day period (Day […]
Adaptive PD-optimal design of a pilot study for a clotting time test for enoxaparin
Background: Dosing of enoxaparin, like other anticoagulants, may result in bleeding following excessive doses and clot formation if the dose is too low. There is no standard measure of enoxaparin clinical effectiveness. We recently showed that a Xa clotting time test could potentially assess the effect of enoxaparin on the clotting system [1]. Preliminary in […]
Evaluation of a Bayesian dose-individualisation method for enoxaparin
Background: Enoxaparin is a low molecular weight heparin used in the treatment of thrombosis. The current approved treatment dose of enoxaparin is based on total body weight and its dosing frequency is based dichotomously on creatinine clearance. Recent evidence has shown these dosing strategies to be suboptimal and Bayesian dose-individualisation has been proposed as a […]
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 […]
Dose Correction for the Michaelis-Menten Approximation of the Target – mediated Drug Disposition Model
Objectives: The target-mediated drug disposition (TMDD) pharmacokinetic (PK) model applies to drugs exhibiting a clearance mechanism due to binding to their targets followed by internalization and degradation [1]. The Michaelis-Menten (M-M) the TMDD PK model was derived based on the rapid binding or quasi steady-state assumptions that implied that the target and drug binding and […]
Pharmacokinetics of methotrexate in red blood cells
Background & Objectives: Low-dose methotrexate (MTX) given once weekly is the gold standard in the therapy of rheumatoid arthritis (RA). However, MTX doses required to achieve adequate disease control are highly variable between patients and difficult to predict. MTX polyglutamate (MTXPG) concentrations inside red blood cells (RBCs) have been discussed as a potential biomeasure predicting […]
What is the best dosing regimen for allopurinol in patients with renal impairment?
Aims To develop a population PKPD model for plasma allopurinol, oxypurinol and serum urate To investigate the best regimen for dosing allopurinol in patients with renal impairment Methods The data were sourced from four studies (one unpublished).1-3 The population analysis was conducted using NONMEM® v.7.2. Covariates analysed included creatinine clearance (as predicted from the Cockcroft-Gault […]
Population Pharmacokinetic Analysis of Ropivacaine and its Metabolite PPX from Pooled Data in Neonates, Infants and Children
Objectives: The aim of the present study was to characterize ropivacaine and PPX pharmacokinetics and factors affecting them in paediatric anaesthesia. Methods: Population pharmacokinetics of ropivacaine and its active metabolite PPX were estimated following single and continuous ropivacaine blocks in 192 patients aged 0-12 years from six pooled published studies. Unbound and total ropivacaine and […]
Meta-modelling
Meta-analysis is an established statistical technique closely associated with systematic reviews of the literature. The concepts of a statistical meta-analysis are increasingly applied to pharmacometric analysis (model-based meta-analysis). The common feature of both approaches is that the experimental “unit” is a publication and they seek to address the problem of small sample sizes. The Central […]