The Influence of Study Design on Identification of True Parameter-Covariate Relationships

Background: Utilisation of D-optimality together with clinical trial simulation are currently the primary methods used to inform clinical trial study designs and facilitate precise estimation of pharmacokinetic-pharmacodynamic (PK-PD) model parameters. A recent simulation study has extended the application of these methods to the qualitative identification of correct covariates [1]. However, the authors did not investigate the […]

Lean Body Weight as a Robust Size Descriptor for Quantifying the Impact of Body Composition on Drug Clearance

Background: Determination of optimal doses for obese patients is challenging due to the paucity of clear dosing guidelines for this population. Empirical dosing strategies based on total body weight (WT) may result in overdoses in the obese, whereas arbitrary dose capping by physicians may produce sub-therapeutic concentrations. Quantifying the impact of obesity on drug clearance using […]

Lean Body Weight versus Total Body Weight as a Covariate for Clearance

Background: When conducting population pharmacokinetic (PK) analyses, total body weight (WT) is often chosen as a covariate to explain between subject variability in clearance (CL). Given that 99% of the body’s clearance takes place within lean tissues, it has been suggested that WT is unlikely to be suitable for obese subjects and lean body weight (LBW) […]