CR TidBit – Allometry

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Allometry, also called biological scaling, the change in organisms in relation to proportional changes in body size.

An example of allometry can be seen in mammals. Ranging from the mouse to the elephant, as the body gets larger, in general hearts beat more slowly, brains get bigger, bones get proportionally shorter and thinner, and life spans lengthen. Even ecologically flexible characteristics, such as population density and the size of home ranges, scale in a predictive way with body size. The study of allometry stems from work in the late 19th century by the Scottish zoologist D’arcy Thompson and in the early 20th century by the English biologist Julian Huxley, the latter of whom coined the term for this field of study.

The entry of a new chemical entity (NCE) into the clinical phase marks an important milestone in its development phase. Part of the planning of the first in man (FIM) study is the prediction and calculation of the first dose mainly based on the analysis of the available preclinical dataset. Some techniques of allometry are currently in use by the pharmaceutical industry, that they are based on the assumption that new characteristics that influence the NCE exposure in plasma or tissues, which were observed in animals or in vitro systems.

Although the aim of an FIM dose prediction is not to cause any adverse events in the human prabands, the 2006 incident after a single dose of Tergenero TGN1412, a monoclonal antibody, resulted in a serious health damage of the study probands. A direct consequence of this serious incidence was a currently draft guideline by Europeam Medicines Agency (EMEA 2007) entitled “Guideline on requirements for FIM clinical trials for potential high risk medicinal products.

Relationships between organ size and body size in growing animals

               log y = α log x + log b

Where x is body size, y is organ size, log b is the intercept of the line on the y-axis and α is the slope of the line, also known as the allometric coefficient. When x and y are body and organ sizes at different developmental stages, the allometric coefficient captures the differential growth ratio between the organ and the body as a whole. When the organ has a higher growth rate than the body as whole, for example, the chela of male fiddler crab, α > 1, which is called positive allometry or hyperallometry. When the organ has a lower growth rate than the body as whole, α < 1, which is called negative allometry or hypoallometry. Organs that have negative allometry include the human head, which grows more slowly than the rest of the body after birth and so is proportionally smaller in adults than in children. When an organ grows at the same rate as the rest of the body, α = 1, a condition called isometry. Such an organ maintains a constant proportionate size (but not absolute size) throughout development.

References: 1. Encyclopedia Britannica, Tobias Pahler. 2. Dose finding in single dose studies by allometry.,Methods in clinical pharmacology ,3. Alexander.W Allometry study of biological scalling, Nature Education knowledge3(10):2.


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