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Abstract
Annual Review of Pharmacology and Toxicology
Vol. 48: 303-332 (Volume publication date February 2008)
(doi:10.1146/annurev.pharmtox.48.113006.094708)
First published online as a Review in Advance on October 3, 2007
Mechanism-Based Concepts of Size and Maturity in Pharmacokinetics

B.J. Anderson1 and N.H.G. Holford2
1Department of Anaesthesiology
2Department of Pharmacology and Clinical Pharmacology, University of Auckland School of Medicine, Auckland, New Zealand; email: ,

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 Emax model (Hill equation) describes gradual maturation of clearance in early life leading to a mature adult clearance achieved at a later age.

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Authors:
B.J. Anderson
N.H.G. Holford
Keywords:
allometry
weight
growth
maturation
postmenstrual age

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