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Quantitative Mechanistic Studies In Simultaneous Fluid Flow And Intestinal Absorption Using Steroids As Model Solutes

I. Komiya, J. Y. Park, A. Kamani, Norman F. H. Ho, W. Higuchi
Published 1980 · Chemistry

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The interplay of flow-rate, aqueous boundary layer and membrane permeability coefficients, solute lipophilicity and intestinal length has been quantitatively determined for the in situ situation of bulk fluid flow and concurrent steady-state absorption of steroids in the small intestines of the rat. Seven steroids ranging in 3 orders of magnitude in n-octanol/water partition coefficients were used. The results followed the physical model predictions described by: C(l)C(0)=exp−2πγlQ·Paq1+PaqPm where ClC(0) is the fraction of steroid remaining in the intestinal lumen of length l, r is the effective lumenal radius, Q is the flow-rate, Paq and Pm are the respective aqueous boundary layer and membrane permeability coefficients. The log fraction of steroids remaining in the lumen was linear with intestinal length at various flow rates. The fraction absorbed increased with slower flow-rates at any given length due to the longer residence time. The fraction of steroid absorbed vs log partition coefficient profiles as a function of flow-rate were significantly sigmoidal. The absorption rates of progesterone were aqueous boundary layer-controlled and the less lipophilic hydrocortisone were membrane-controlled. It is significant that the permeability of the aqueous boundary layer is proportional to Q0.44.
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This paper is referenced by
Effect of intestinal fluid flux on ibuprofen absorption in the rat intestine.
M. Lane (2006)
Drug absorption sites in the gastrointestinal tract and dosage forms for site-specific delivery
N. Rouge (1996)
Evolutionary combinatorial chemistry, a novel tool for SAR studies on peptide transport across the blood–brain barrier. Part 2. Design, synthesis and evaluation of a first generation of peptides
M. Teixidó (2005)
Intestinal permeability studies of sulpiride incorporated into self-microemulsifying drug delivery system (SMEDDS).
Mallikarjun Chitneni (2011)
How structural features influence the biomembrane permeability of peptides.
P. S. Burton (1996)
In situ jejunal uptake from liposomal systems
D. Schwinke (1984)
Passive Absorption of Drugs in Caco-2 Cells
P. Artursson (1991)
Studies on drug absorption from oral cavity. II. Influence of the unstirred water layer on absorption from hamster cheek pouch in vitro and in vivo.
Y. Kurosaki (1987)
A method for the determination of cellular permeability coefficients and aqueous boundary layer thickness in monolayers of intestinal epithelial caco 2 cells grown in permeable filter chambers
J. Karlsson (1991)
Development and Characterization of a Novel Mouse Line Humanized for the Intestinal Peptide Transporter PEPT1
Y. Hu (2014)
Intestinal permeability of metformin using single-pass intestinal perfusion in rats.
Nai-ning Song (2006)
Drug–Membrane Interaction on Immobilized Liposome Chromatography Compared to Immobilized Artificial Membrane (IAM), Liposome/Water, and Octan‐1‐ol/Water Systems
X. Liu (2010)
Evaluation of Permeability and P-glycoprotein Interactions: Industry Outlook
P. Balimane (2008)
The Mucosa of the Small Intestine
M. Doherty (2002)
Design of prodrugs for improved gastrointestinal absorption by intestinal enzyme targeting.
D. Fleisher (1985)
Determination of the membrane permeability coefficient and the reflection coefficient by the two-dimensional laminar flow model for intestinal perfusion experiments.
Y. Miyamoto (1986)
Active Secretion of Drugs from the Small Intestinal Epithelium in Rats by P‐Glycoprotein Functioning as an Absorption Barrier
T. Terao (1996)
Retinoid absorption from simple and mixed micelles in the rat intestine.
Y. K. Pithavala (1995)
In Vivo Permeability Studies in the Gastrointestinal Tract of Humans
N. Petri (2008)
P. Z. Milani (2009)
Intestinal permeability of chlorpyrifos using the single-pass intestinal perfusion method in the rat.
T. Cook (2003)
A Drug Absorption Model Based on the Mucus Layer Producing Human Intestinal Goblet Cell Line HT29-H
A. Wikman (2004)
In vitro measurement of drug transport using a new diffusion chamber compatible with Millicell® culture supports : performance with caco-2 monolayers
M. T. Kuhfeld (1996)
A drug absorption model of the intestinal tract based on the two-dimensional laminar flow in a circular tube.
Y. Miyamoto (1982)
Optimization of the local inhibition of intestinal adenosine deaminase (ADA) by erythro-9-(2-hydroxy-3-nonyl)adenine: enhanced oral delivery of an ADA-activated prodrug for anti-HIV therapy.
D. Singhal (1998)
Absorption and intestinal metabolism of purine dideoxynucleosides and an adenosine deaminase-activated prodrug of 2',3'-dideoxyinosine in the mesenteric vein cannulated rat ileum.
D. Singhal (1998)
The Effect of a Drug‐delivery System Consisting of Soybean Phosphatidyl Choline and Medium‐chain Monoacylglycerol on the Intestinal Permeability of Hexarelin in the Rat
U. Fagerholm (1998)
The effect of mixed micellar systems, bile salt/fatty acids, on the solubility and intestinal absorption of clofazimine (B663) in the anaesthetised rat
J. R. O'Reilly (1994)
An in vitro method for predicting in vivo oral bioavailability of novel immunosuppressive drugs.
V. Dias (1996)
Investigation of the intestinal permeability of ciclosporin using the in situ technique in rats and the relevance of P-glycoprotein.
P. Zakeri-Milani (2008)
Absorption of iothalamate after oral administration and absorption enhancement by amino acids in dogs and rats.
T. Prueksaritanont (1986)
Lipophilicity measurement of drugs by reversed phase HPLC over Wide pH range using an alkaline-resistant silica-based stationary phase, XBridge Shield RP(18).
X. Liu (2008)
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