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 […]
2012
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regimen for dosing allopurinol in patients with renal impairment Methods The data were sourced from four studies (one unpublished).1-3 The population analysis was conducted using NONMEM® v.7.2.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 […]