Allometric

West GB, Woodruff WH, Brown JH. Allometric scaling of metabolic rate from molecules and mitochondria to cells and mammals. Proc Natl Acad Sci USA 2002 99 Suppl 1 2473-8. 

A hallmark of PB-PK models is the ability to scale up animal-based models to humans, thus allowing tissue drug concentrations to be predicted in the absence of data that are difficult or impossible to collect. Initial efforts to apply interspecies extrapolations to anticancer drugs have been greatly extended to chemical risk assessment based on PB-PK models [14]. Empirical allometric equations based on animal body weight have been the mainstay to scale organ weights and... 

Table 2. Allometric equations used in this chapter.

Gehring C, Park S, Denicha M. Liana allometric biomass equations for Amazonian primary and secondary forest. Forest ecology and management, 2004. 195 pp. 69-83. doi 10.1016/j.foreco.2004.02.054... 

K, logistic growth curve constant K, logistic growth curve constant Volume, allometric exponents Liver Kidney Bone... 

The limitations of allometric scaling led us to investigate the method of effect scaling as an alternative strategy for matching equivalent doses of MDMA in rats and humans. In this approach,... 

The allometric coefficient and exponent are determined empirically, and are not thought to have any physiological correlate. 

Unfortunately, when clearance is largely metabolic and low, allometry can significantly over-predict the human value [71]. Recent investigations have attempted to address this by combining allometric approaches with in vitro metabolism data [5],... 

A recent debate on allometric scaling has suggested that a great deal of further work is necessary before allometry can be used with confidence in a prospective... 

As described above, it will be normal to assume that the dose interval is 24 hours, i.e., once-a-day dosing. Absorption can be estimated with good confidence from absorption in the rat (see Section 6.1). Clearance is the sum of the predicted hepatic, renal, biliary and extrahepatic clearance. Hepatic clearance can be derived from in vitro studies with the appropriate human system, using either microsomes or hepatocytes. We prefer to use an approach based on that described by Houston and Carlile [83], Renal clearance can be predicted allometrically (see section 6.8.1). The other two potential methods of clearance are difficult to predict. To minimize the risks, animal studies can be used to select compounds that show little or no potential for clearance by these routes. As volume can be predicted from that measured in the dog, after correction for human and dog plasma protein binding (see Section 6.2), it is possible to make predictions for all of the important parameters necessary. 

We believe that this approach brings together the best combination of in vitro to in vivo and allometric approaches, and can provide useful estimates of likely human doses, provided that sufficient attention is paid to the errors associated with all of the measurements [4]. 

Lave, T., Coassolo, P., Reigner, B., Prediction of hepatic metabolic clearance based on interspecies allometric scaling techniques and in vitro-in vivo correlations, Clin. Pharmacokinet. 1999, 36, 211-321 and references cited therein. 

Boxenbaum, H., DiLea, C., First-time-in-human dose selection allometric... 

Jezequel, S. G., Fluconazole interspecies scaling and allometric relationships of pharmacokinetic properties, J. Pharm. Pharmacol. 1994, 46, 196-199. 

Bonate, P. L., Howard D., Critique of prospective allometric scaling does the emperor have clothes J. Clin. Pharmacol. 2000, 40, 335—340. 

Prediction methods based on animal pharmacokinetic data can be categorized into three types (1) allometric scaling, (2) proportionality methods, and (3) correlative approaches. All three make a basic underlying assumption that the types... 

A recent variation on the prediction of human VD using allometric scaling involves the use of what has been termed "fractal volume of distribution (vf) [7], This refers to the VD value corrected to within the bounds of actual volumes within the body - in the case of human the upper and lower bounds would be 70 1 and plasma volume, respectively. Thus, even if a compound were to have a VDSS of 1000 1, its Vf would be 69.8 1. The authors of this approach have shown that Vf scales allometrically across species better than VD [8], with the explanation that body volume and body mass are exactly scaleable across species. Animal values for Vf are calculated from VD obtained from pharmacokinetic studies using the relationship ... 

Stone KC, Mercer RR, Gehr P, Stockstill B, Crapo JD (1992) Allometric relationships of cell numbers and size in the mammalian lung. Am J Respir Cell Mol Biol 6 235-243... 

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