Nicholas H G Holford1, Thierry Buclin. 1. Department of Pharmacology & Clinical Pharmacology, University of Auckland, Auckland, New Zealand. n.holford@auckland.ac.nz
Abstract
BACKGROUND: A primary goal of clinical pharmacology is to understand the factors that determine the dose-effect relationship and to use this knowledge to individualize drug dose. METHODS: A principle-based criterion is proposed for deciding among alternative individualization methods. RESULTS: Safe and effective variability defines the maximum acceptable population variability in drug concentration around the population average. CONCLUSIONS: A decision on whether patient covariates alone are sufficient, or whether therapeutic drug monitoring in combination with target concentration intervention is needed, can be made by comparing the remaining population variability after a particular dosing method with the safe and effective variability.
BACKGROUND: A primary goal of clinical pharmacology is to understand the factors that determine the dose-effect relationship and to use this knowledge to individualize drug dose. METHODS: A principle-based criterion is proposed for deciding among alternative individualization methods. RESULTS: Safe and effective variability defines the maximum acceptable population variability in drug concentration around the population average. CONCLUSIONS: A decision on whether patient covariates alone are sufficient, or whether therapeutic drug monitoring in combination with target concentration intervention is needed, can be made by comparing the remaining population variability after a particular dosing method with the safe and effective variability.
Authors: Francisco J Diaz; Michel J Berg; Ron Krebill; Timothy Welty; Barry E Gidal; Rita Alloway; Michael Privitera Journal: Clin Pharmacokinet Date: 2013-12 Impact factor: 6.447
Authors: Jeannine S McCune; Meagan J Bemer; Jeffrey S Barrett; K Scott Baker; Alan S Gamis; Nicholas H G Holford Journal: Clin Cancer Res Date: 2013-11-11 Impact factor: 12.531