Journal ArticleDOI
Regional jejunal perfusion, a new in vivo approach to study oral drug absorption in man.
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It was shown that it was possible to establish a tight intestinal segment which behaved as a well-mixed compartment and the low perfusion rate of 3 ml/min was preferred, since it resulted in the lowest variability in absorption.Abstract:
Recently a new in vivo approach in man, using a regional intestinal perfusion technique, has been developed. The perfusion tube consists of a multichannel tube with two inflatable balloons, which are placed 10 cm apart. The tube is introduced orally and the time required for insertion and positioning of the tube is approximately 1 hr. In the present study eight healthy subjects were perfused in the proximal jejunum on three separate occasions. The first two perfusion experiments used the same flow rate, 3 ml/min, and the third experiment used 6 ml/min. Phenazone (antipyrine) was chosen as the model drug. The recovery of PEG 4000 in the outlet intestinal perfusate was complete in experiments 1 and 2, but slightly lower (90%) when the higher flow rate was used. The mean (+/- SD) fraction of phenazone absorbed calculated from perfusion data was 51 +/- 12% (3 ml/min), 64 +/- 19% (3 ml/min), and 42 +/- 27% (6 ml/min) for the three experiments, respectively. The mean fraction absorbed estimated by deconvolution of the plasma data was 47 +/- 16%, 51 +/- 19%, and 38 +/- 26%, respectively. The effective permeability of phenazone was 5.3 +/- 2.5, 11 +/- 6.8, and 11 +/- 12 (x 10(4) cm/sec, respectively. We have shown that it was possible to establish a tight intestinal segment which behaved as a well-mixed compartment. The low perfusion rate of 3 ml/min was preferred, since it resulted in the lowest variability in absorption.(ABSTRACT TRUNCATED AT 250 WORDS)read more
Citations
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A Theoretical Basis for a Biopharmaceutic Drug Classification: The Correlation of in Vitro Drug Product Dissolution and in Vivo Bioavailability
TL;DR: A biopharmaceutics drug classification scheme for correlating in vitro drug product dissolution and in vivo bioavailability is proposed based on recognizing that drug dissolution and gastrointestinal permeability are the fundamental parameters controlling rate and extent of drug absorption.
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Caco-2 monolayers in experimental and theoretical predictions of drug transport
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Dissolution Testing as a Prognostic Tool for Oral Drug Absorption: Immediate Release Dosage Forms
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Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors. Similarities and differences.
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References
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Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells
Per Artursson,Johan Karlsson +1 more
TL;DR: The results indicate that Caco-2 monolayers can be used as a model for studies on intestinal drug absorption and a good correlation was obtained between data on oral absorption in humans and the results in the Cco-2 model.
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Studies of Intestinal Digestion and Absorption in the Human
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Contribution of solvent drag through intercellular junctions to absorption of nutrients by the small intestine of the rat
J. R. Pappenheimer,K Z Reiss +1 more
TL;DR: It is proposed that Na-coupled transport of organic solutes from lumen to inter cellular spaces provides the principal osmotic force for fluid absorption and triggers widening of intercellular junctions, thus promoting bulk absorption of nutrients by solvent drag.
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Estimating Human Oral Fraction Dose Absorbed: A Correlation Using Rat Intestinal Membrane Permeability for Passive and Carrier-Mediated Compounds
TL;DR: The correlation between fraction dose absorbed in humans and Pw* determined from steady-state perfused rat intestinal segments gives an excellent correlation, indicating that Pw*, is one of the key variables controlling oral drug absorption and that the correlation may be useful for estimating oral drugabsorption in humans regardless of the mechanism of absorption.
Journal ArticleDOI
Alteration of intestinal tight junction structure and permeability by cytoskeletal contraction
TL;DR: The data tie CD elicited alterations in tight junction structure and permeability to an energy dependent event that appears to be PAMR contraction, and it is speculated that tensile forces within the PamR regulate tight junction structures and function.