Biomaterial Database

Interspecies scaling: predicting clearance of drugs in humans. Three different approaches. 1996

I Mahmood, and J D Balian

Division of Pharmaceutical Evaluation I. Food & Drug Administration, Rockville, MD 20852, USA.

1. The interspecies scaling approach to predict clearance in humans from animal data was tested for a wide variety of drugs. 2. Three different methods were utilized to generate plots to scale-up the clearance values: (i) method I, clearance versus body weight (simple allometric equation); (ii) method II, product of clearance and maximum life-span potential; (iii) method III, product of clearance and brain weight versus body weight. 3. The circumstances under which the three methods can be applied to predict clearance in humans were evaluated. 4. If the exponent lies between 0.55 to 0.7 then method I predicts clearance reasonably well. 5. If the exponent lies between 0.71 to 1.0 clearance can be predicted reasonably well by method II. 6. If the exponent is > 1.0 clearance can be predicted using method III.

UI	MeSH Term	Description	Entries
D008433	Mathematics	The deductive study of shape, quantity, and dependence. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)	Mathematic
D008657	Metabolic Clearance Rate	Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site.	Total Body Clearance Rate,Clearance Rate, Metabolic,Clearance Rates, Metabolic,Metabolic Clearance Rates,Rate, Metabolic Clearance,Rates, Metabolic Clearance
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
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