Document Detail


Potential error in the measurement of tissue to blood distribution coefficients in physiological pharmacokinetic modeling. Residual tissue blood. I. Theoretical considerations.
MedLine Citation:
PMID:  1676658     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Physiological pharmacokinetic models require the determination of tissue to blood distribution coefficients. A theoretical model has been developed and the resulting equations indicate that under certain conditions it is necessary to correct for the presence of drug in the residual blood remaining in the tissue. The potential error in ignoring this residual blood is expressed mathematically in terms of several important factors that include the anatomical features of the tissue (volume fractions of the blood, interstitial fluid, and cellular space) as well as the physicochemical properties of the drug (extent of binding in the blood and tissues). These theoretical considerations and resulting simulations have been applied to experimental literature data for several compounds (methotrexate, digoxin, and biperiden). We conclude that correction for the residual blood is necessary when the values of tissue to blood distribution coefficients are very small or large (relative to one) and when the volume fraction of the blood in tissue is substantial.
Authors:
S P Khor; M Mayersohn
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Drug metabolism and disposition: the biological fate of chemicals     Volume:  19     ISSN:  0090-9556     ISO Abbreviation:  Drug Metab. Dispos.     Publication Date:    1991 Mar-Apr
Date Detail:
Created Date:  1991-08-14     Completed Date:  1991-08-14     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9421550     Medline TA:  Drug Metab Dispos     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  478-85     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutical Sciences, College of Pharmacy, University of Arizona, Tucson 85721.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biperiden / pharmacokinetics
Blood / metabolism*
Chemistry, Physical
Digoxin / pharmacokinetics
Humans
Methotrexate / pharmacokinetics
Models, Biological*
Pharmacokinetics*
Physicochemical Phenomena
Rats
Tissue Distribution
Grant Support
ID/Acronym/Agency:
DA02680/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
20830-75-5/Digoxin; 514-65-8/Biperiden; 59-05-2/Methotrexate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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