Document Detail


An in vitro pulmonary permeation system with simulation of respiratory dynamics.
MedLine Citation:
PMID:  11485178     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To study the effect of respiration on transpulmonary permeation kinetics of drugs, an in vitro pulmonary permeation system, which consists of a setup for the simulation of respiratory dynamics, was developed. The system is composed offour major components: a pair of horizontal-type half-cells, a model air-blood barrier, an instrument for the application and regulation of respiratory pressure, and a pressure monitoring system. Calibration studies were performed and results showed that the primary respiration parameters (the peak inspiration pressure, respiratory frequency, and the percent inspiration time) can be controlled at a reproducible manner. This system appears to simulate very well the respiratory dynamics observed normally under physiologic conditions. After calibration, the system was utilized to characterize and quantitate the effect of respiration on the transpulmonary permeation of drugs using progesterone as the model drug. The results showed that progesterone permeability is increased as much as 1.8-5.6 folds by application of a respiratory pressure, depending on the combination of respiration parameters. Further studies demonstrated that the enhancement in pulmonary permeation triggered by respiratory pressure is resulted from the stretching of the lung tissue, not by the pressure gradient itself. The observations lead to the conclusion that the system developed in this investigation is a useful in vitro tool for studying the kinetics of pulmonary drug permeation under a physiologically simulating respiratory dynamics. The studies have provided scientific evidence for demonstrating that respiration is an important factor in determining the kinetics of transpulmonary drug permeation through possible alteration in the properties of the air-blood barrier.
Authors:
J Yu; Y W Chien
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Validation Studies    
Journal Detail:
Title:  Pharmaceutical development and technology     Volume:  6     ISSN:  1083-7450     ISO Abbreviation:  Pharm Dev Technol     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-08-03     Completed Date:  2002-01-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9610932     Medline TA:  Pharm Dev Technol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  363-71     Citation Subset:  IM    
Affiliation:
Controlled Drug-Delivery Research Center, Rutgers University, New Brunswick, NJ 08906-0406, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Membrane Permeability / physiology
Lung / blood supply,  metabolism,  physiology*
Progesterone / pharmacokinetics
Rana catesbeiana
Respiratory Mechanics / physiology*
Respiratory Mucosa / blood supply,  metabolism,  physiology
Transducers, Pressure
Ventilators, Mechanical
Chemical
Reg. No./Substance:
57-83-0/Progesterone

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


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