Document Detail


Lymphatic transport of proteins after s.c. injection: implications of animal model selection.
MedLine Citation:
PMID:  11489338     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Subcutaneous (s.c.) administration continues to be the main route for the delivery of protein drugs due to their poor bioavailability by most non-parenteral routes. While small drug molecules are rapidly and extensively absorbed after s.c. injection, the systemic bioavailability of protein drugs is often incomplete and variable. Given the widespread use of the s.c. route for protein drugs, surprisingly little is known about the factors that govern the rate and extent of protein absorption from the interstitial space and the role of the lymphatic system in the transport of these molecules to the systemic circulation. The few studies that have directly addressed the role of lymphatic transport in protein bioavailability are complicated by the use of methods and models that vary widely. In this review we will evaluate the available literature describing the lymphatic transport of proteins after s.c. injection and more specifically, address the impact of experimental variation (e.g. site of cannulation, animal model, anesthesia) on the interpretation of the data obtained. We will also describe in some detail the sheep model currently in use in our laboratory, which allows both estimation of the extent of uptake of protein drugs into the lymphatics draining the injection site, and quantification of the contribution of lymphatic transport to the absolute bioavailability.
Authors:
C J Porter; G A Edwards; S A Charman
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Advanced drug delivery reviews     Volume:  50     ISSN:  0169-409X     ISO Abbreviation:  Adv. Drug Deliv. Rev.     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-08-07     Completed Date:  2001-10-04     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  8710523     Medline TA:  Adv Drug Deliv Rev     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  157-71     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutics, Victorian College of Pharmacy, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Vic. 3052, Australia. chris.porter@vcp.monash.edu.au
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MeSH Terms
Descriptor/Qualifier:
Animals
Humans
Injections, Subcutaneous
Lymphatic System / metabolism*
Proteins / administration & dosage,  metabolism*
Species Specificity
Chemical
Reg. No./Substance:
0/Proteins

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


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