Species Scaling

Oral unbound clearance (i.e. oral clearance correct for free fraction) 

Fraction of unbound drag in tissues Natural logarithm Organ blood flow 

Ratio of binding proteins in extracellular fluid (except plasma) to binding proteins in plasma Correlation coefficient Elimination half-life Volume of distribution Volume of extracellular fluid Volume of plasma Volume of remaining fluid 

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Species Scaling Adjusting for Maximum Life Span Potential... 

Species Scaling Incorporating Differences in Metabolic Clearance... 

Inter-Species Scaling for Clearance by Hepatic Uptake... 

Another approach to dosimetry correction may be that used by EPA when extrapolating from animal cancer bioassays to theoretical excess human cancer risk levels for lifetime exposures (EPA 1992). The cross species scaling factor used is based on an equivalence of mg/kg /day. There is reasonable scientific support for utilizing this approach based on an analysis of a number of multi... 

How rapidly diffusion occurs is characterized by the diffusion coefficient D, a parameter that provides a measure of the mean of the squared displacement x of a molecule per unit time f. For diffusion in two dimensions such as a membrane, this is given by = 4Ht. The Saffman-Delbrtlck model of Brownian motion in biologic membranes describes the relationship between membrane viscosity, solvent viscosity, the radius R and height of the diffusing species, and D for both lateral and rotational diffusion of proteins in membranes (3, 4). This model predicts for example that for lateral diffusion, D should be relatively insensitive to the radius of the diffusing species, scaling with log (1/R). 

Ings RMJ. Inter species scaling and comparisons in drug development and toxicokinetics. Xenobiotica 1990 20 1201-31. 

Eactors to be considered in deciding whether or not inter species scaling would be predictive of human PK parameter estimates include (1) binding characteristics/ (2) receptor density/ (3) size and charge of molecule/ (4) end-terminal carbohydrate characteristics/ (5) degree of sialylatioii/ and (6) saturation of elimination pathways. These factors are known to influence clearance and distribution volumes/ as will be discussed in subsequent sections. Por example/ clearance may involve several mechanisms/ including immune-mediated clearance that results in nonconstant clearance rates. The interspecies predictability of clearance in this situation would be questionable. 

Mordent J, Chen SA, Moore JA, Ferraiolo BL, Green JD. In ter species scaling of clearance and volume of distribution data for five therapeutic proteins. Pharm Res 1991 8 1351-9. 

EPA (US Environmental Protection Agency) (1992). Draft report A cross-species scaling factor for carcinogen risk assessment based on equivalence of mg/kg /day Notice. Fed Reg 57, 24152-24173. 

Each term is proportional to the surface coverage by the respective species, scaled so that the leading " 1" is proportional to the vacant surface, and n is the number of sites involved in the molecular reaction. Some reactions require substitutions in eqn 9.7. A tabulation of groups and substitutions is shown on the next two pages. 

Ethyl N-[2-(p-phenoxyphenoxy)ethyl]carbamate (Ro 13-5223, fenoxycarb, 56), a compound possessing high juvenile hormone activity, has gained practical importance in the control of various lepidopterous species, scale insects, fire ants and stored product pests (Fischer eta/., 1980 Masnere/a/., 1981 Dome/a/., 1981). It completely inhibits the population growth of the California red scale, Aonidiella aurantii in a concentration as low as 0.03%. It interrupts the development during morphogenesis and thus prevents eclosion of adults. 

Allometry is an empirical approach to predicting pharmacokinetic parameters across species. It has developed from a much wider discipline that correlates shape to a power-function of some measure of size or mass. For example, Kleibers law states that the basal metabolic rate across animal species scales to the power 0.75 to body weight. ... 

The energy for the absorption maxima, max obtained from thiophene oligomers in a neutral state, radical cation form and bicationic species scales... 

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