The allometric approach for interspecies scaling of pharmacokinetic parameters. 1992

W A Ritschel, and N N Vachharajani, and R D Johnson, and A S Hussain
Division of Pharmaceutics and Drug Delivery Systems, College of Pharmacy, University of Cincinnati Medical Center, OH 45267-004.

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."

UI MeSH Term Description Entries
D008017 Life Expectancy Based on known statistical data, the number of years which any person of a given age may reasonably be expected to live. Life Extension,Years of Potential Life Lost,Expectancies, Life,Expectancy, Life,Life Expectancies
D009929 Organ Size The measurement of an organ in volume, mass, or heaviness. Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D010599 Pharmacokinetics Dynamic and kinetic mechanisms of exogenous chemical DRUG LIBERATION; ABSORPTION; BIOLOGICAL TRANSPORT; TISSUE DISTRIBUTION; BIOTRANSFORMATION; elimination; and DRUG TOXICITY as a function of dosage, and rate of METABOLISM. LADMER, ADME and ADMET are abbreviations for liberation, absorption, distribution, metabolism, elimination, and toxicology. ADME,ADME-Tox,ADMET,Absorption, Distribution, Metabolism, Elimination, and Toxicology,Absorption, Distribution, Metabolism, and Elimination,Drug Kinetics,Kinetics, Drug,LADMER,Liberation, Absorption, Distribution, Metabolism, Elimination, and Response
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013045 Species Specificity The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species. Species Specificities,Specificities, Species,Specificity, Species

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