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Drug Metabolism and Pharmacokinetics
Article . 2009 . Peer-reviewed
License: Elsevier TDM
Data sources: Crossref
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Mechanistic Basis of Using Body Size and Maturation to Predict Clearance in Humans

Authors: ANDERSON, Brian J.; HOLFORD, Nick H. G.;

Mechanistic Basis of Using Body Size and Maturation to Predict Clearance in Humans

Abstract

Growth and development are two major aspects of children not readily apparent in adults. Clearance in the paediatric population should be investigated using models that describe size, maturation and organ function influences. Size is the primary covariate and although lean body weight is argued as a better measure than total body weight, the use of different fractions of fat mass to explain how pharmacokinetic parameters vary with body composition has been proposed. Allometric scaling using an empiric power exponent of 3/4 is superior to scaling using body surface area. The sigmoid hyperbolic model has proven useful to describe maturation. An extra parameter that describes asymmetry can be incorporated into this model. These descriptors are used to illustrate creatinine, morphine and paracetamol clearance in children. Simultaneous investigation of pooled GFR, paracetamol and morphine data enabled testing for shared common features of maturation processes. Results suggest that GFR matures before paracetamol or morphine clearance, consistent with phase II conjugation processes that convert xenobiotics to water soluble forms that can subsequently be eliminated from the body through the renal system. The use of such mechanistic approaches improves understanding of paediatric pharmacokinetics; improving dosing predictions and allowing projection in exploratory drug development.

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Keywords

body composition, Aging, Morphine, maturation, Body Surface Area, clearance, Kidney, size, Models, Biological, Metabolic Detoxication, Phase II, Liver, Pharmaceutical Preparations, Predictive Value of Tests, Animals, Body Size, Humans, Metabolic Detoxication, Phase I, pharmacokinetics, Acetaminophen, Glomerular Filtration Rate

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    458
    popularity
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    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
458
Top 1%
Top 1%
Top 1%
gold