Document Detail

Interspecies scaling: role of protein binding in the prediction of clearance from animals to humans.
MedLine Citation:
PMID:  11185664     Owner:  NLM     Status:  MEDLINE    
The objective of this study is to evaluate whether unbound clearance of a drug can be predicted more accurately than total clearance using the allometric approach and if there is any real advantage of predicting unbound clearance over total clearance. The total and unbound clearance of 20 randomly selected drugs were scaled up from the animal data (at least three animal species) obtained from the literature. Three methods were used to generate plots to scale up the clearance values: (1) total or unbound clearance versus body weight (simple allometric equation), (2) the product of total or unbound clearance and maximum life span potential (MLP) versus body weight, and (3) the product of total or unbound clearance and brain weight versus body weight. The results of this study indicate that there will be instances when unbound clearance can be predicted better than total clearance or vice versa. In conclusion, unbound clearance cannot be predicted any better than total clearance.
I Mahmood
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of clinical pharmacology     Volume:  40     ISSN:  0091-2700     ISO Abbreviation:  J Clin Pharmacol     Publication Date:  2000 Dec 
Date Detail:
Created Date:  2000-12-11     Completed Date:  2000-12-22     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  0366372     Medline TA:  J Clin Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1439-46     Citation Subset:  IM    
Division of Pharmaceutical Evaluation I, Office of Clinical Pharmacology and Biopharmaceutics, Food and Drug Administration, Rockville, Maryland 20852, USA.
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MeSH Terms
Drug Design*
Metabolic Clearance Rate
Models, Animal
Protein Binding
Species Specificity

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