Document Detail

Solute absorption from the airways of the isolated rat lung. IV. Mechanisms of absorption of fluorophore-labeled poly-alpha,beta-[N(2-hydroxyethyl)-DL-aspartamide]
MedLine Citation:
PMID:  8165179     Owner:  NLM     Status:  MEDLINE    
The pulmonary absorption kinetics of a single molecular weight distribution (MWD) of fluorophore-labeled poly-alpha,beta-[N(2-hydroxyethyl)-DL-aspartamide] (F-PHEA), a hydrophilic and biocompatible synthetic polypeptide, were studied in the isolated, perfused rat lung (iprl) as functions of administered polymer concentration, dose, vehicle, and presence and absence of fluorophore. The MWD was characterized before and after absorption by measurement of weight- and number-averaged molecular weights (Mw and Mn, respectively) using high-performance gel-permeation chromatography. Values for Mw and Mn were 8.6 and 5.3 kD before, and 6.7 and 4.7 kD after, absorption into the perfusate; there was no significant metabolism and the MWD of the absorbed polymer was independent of both dose and sampling time over a 3-hr period. F-PHEA failed to show any evidence of aggregation in solution or changes in dose distribution within the airways as functions of increasing polymer concentration and dose. A concentration ranging study indicated the presence of a saturable, carrier-mediated transport process for F-PHEA with a maximum absorption rate, Vmax, of approximately 180 micrograms or 0.027 mumol/hr. Coadministration of fluorophore-free PHEA was capable of depressing the absorption of F-PHEA. The transport process for F-PHEA appeared to have a molecular weight limit of about 7 kD for this hydrophilic polymer.
P R Byron; Z Sun; H Katayama; F Rypacek
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pharmaceutical research     Volume:  11     ISSN:  0724-8741     ISO Abbreviation:  Pharm. Res.     Publication Date:  1994 Feb 
Date Detail:
Created Date:  1994-05-24     Completed Date:  1994-05-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  221-5     Citation Subset:  IM    
Aerosol Research Group, School of Pharmacy, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0533.
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MeSH Terms
Dose-Response Relationship, Drug
Drug Carriers
Fluorescent Dyes
Lung / metabolism*
Molecular Weight
Peptides / administration & dosage,  pharmacokinetics*
Regression Analysis
Tissue Distribution
Trachea / drug effects
Reg. No./Substance:
0/Drug Carriers; 0/Fluorescent Dyes; 0/Peptides; 0/Polymers; 0/alpha,beta-poly((2-hydroxyethyl)-aspartamide)

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