Toxicology Research Today is a free monthly online journal that collates and summarizes the latest research about Toxicology, including details on forensic toxicology, carcinogenicity, assays.

Mechanism-Based Concepts of Size and Maturity in Pharmacokinetics.

Anderson BJ, Holford NH

Department of Anaesthesiology, University of Auckland School of Medicine, Auckland, New Zealand briana@adhb.govt.nz.

blacksquare, square, filled Abstract Growth and development can be investigated using readily observable demographic factors such as weight and age. Size is the primary covariate and can be referenced to a 70-kg person with allometry using a coefficient of 0.75 for clearance and 1 for volume. The use of these coefficients is supported by fractal geometric concepts and observations from diverse areas in biology. Fat free mass (FFM) might be expected to do better than total body weight when there are wide variations in fat affecting body composition. Clearance pathways develop in the fetus before birth. The use of postnatal age as a descriptor of maturation is unsatisfactory because birth may occur prematurely; therefore postmenstrual age is a superior predictor of elimination function. A sigmoid E(max) model (Hill equation) describes gradual maturation of clearance in early life leading to a mature adult clearance achieved at a later age. Expected final online publication date for the Annual Review of Pharmacology and Toxicology Volume 48 is January 6, 2008. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.

Published 4 October 2007 in Annu Rev Pharmacol Toxicol.
Full-text of this article is available online (may require subscription).

© 2005-2008 Toxicology Research Today. All Rights Reserved.