The allometric approach for interspecies scaling of pharmacokinetic parameters.

A long standing problem in pharmacokinetics and toxicology is the extrapolation and correlation between results obtained in different animal species and man. Animal data may be scaled-up to predict PPs in man using the allometric approach. The allometric approach is empirical, but easy, and is based on the fact that the underlying physiological processes such as blood flow, heartbeat duration, breath duration etc. are essentially physical and related to B. This approach is generally applicable to compounds that are essentially renally excreted. For substances that are highly extracted by the liver, Cltot is a function of the LBF among various species. Based on the concept of neoteny, use of brain weight affords a more correct approach to the scaling of Cl(int) of low extraction ratio drugs. By using the invariant pharmacokinetic time, the superficial differences in concentration-time profiles due to chronological time among different species are removed. Finally, as Boxenbaum (1984) has said "parameters to be scaled, independent variables, and the mathematical relationships used in the scaling process are all at the discretion of the investigator. There are no proper or improper approaches; the only limitations are those imposed by the investigator."