Allometric scaling 4341 Subject

First, if the compound was cleared mainly by hepatic metabolism in the animal species tested and if human hepatocytes in vitro suggest the same will be true in humans, then the measured hepatocyte clearance may be used in a process called in vitro/in vivo scaling (20, pp. 207-228) to provide an estimate of the human intrinsic clearance. The application of Equation 5 then gives an estimate of the human systemic clearance. Second, the animal PK parameters of CL and Vj can be subjected to allometric scaling (20, pp. 207-228) whereby the PK parameter is related to a measurable allometric variable such as body mass, body surface area, heart rate, and so forth. (21) by fitting these parameter-variable pairs for several species to an empirical power equation of the form... 

Bartlett, M.S., 1949. Fitting a straight line when both variables are subject to error. Biometrics 5, 207-212. Demetrius, L., 2006. The origin of allometric scaling laws in biology. J. Theor. Biol. 243, 455-467. 

To predict hepatic clearance of Compound X in man, human in vitro intrinsic clearance could then be scaled to hepatic clearance, using a technique that had been validated in the rat. Ashfortt et al 1995Renal clearance is subject to an allometric relationship and can generally be scaled across species (see below). The predicted in vivo renal Cl for the rat (estimated by multiplying the predicted hepatic Cl by 9) may be scaled allometrically to... 

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