Physiological measurements of luminal stirring in the dog and human small bowel.

Levitt, Michael D.; Furne, Julie; Strocchi, Alessandra; Anderson, B. W.; Levitt, David G.

doi:10.1172/jci114873

Cited by 64 publications

(40 citation statements)

References 27 publications

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“…As discussed above, the observed hydrolysis of low concentrations of maltose in the rat could not have occurred if the unstirred layer over the villous tips had been thicker than ‫ف‬ 20 m. Analysis of the absorption of low glucose concentrations in man indicated that the observed absorption rates could not have occurred if the unstirred layer were greater than 40-m thick (13). In contrast, very slowly absorbed solutes would diffuse the entire length of the intervillous space, about 600 m in man.…”

Section: Discussionmentioning

confidence: 95%

Use of maltose hydrolysis measurements to characterize the interaction between the aqueous diffusion barrier and the epithelium in the rat jejunum.

Levitt

Fine²,

Furne³

et al. 1996

J. Clin. Invest.

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Rates of intestinal absorption and surface hydrolysis are determined by the interaction of two barriers: poorly stirred fluid adjacent to the mucosa, and the epithelial cell. These two barriers commonly are modeled as a fixed, flat layer of epithelium covered by a fixed thickness of unstirred fluid. To more accurately simulate these barriers in a villous mucosa, maltase activity (measured in vitro) was distributed over an anatomically correct model of rat jejunal villi. We then determined what interaction of the aqueous and epithelial barriers best predicted in vivo maltose hydrolysis rates measured over a broad range of infusate concentrations.

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Section: Discussionmentioning

confidence: 95%

Use of maltose hydrolysis measurements to characterize the interaction between the aqueous diffusion barrier and the epithelium in the rat jejunum.

Levitt

Fine²,

Furne³

et al. 1996

J. Clin. Invest.

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“…Using the effective intestinal membrane permeability of glucose in dogs (16×10 −4 cm/s) (15), the permeation of which is rate-limited by UWL, the thickness of the diffusion layer of UWL is expressed by Eq. 3 below (6).…”

Section: Calculation Of Unstirred Water Layer Permeabilitymentioning

confidence: 99%

Rate-Limiting Steps of Oral Absorption for Poorly Water-Soluble Drugs in Dogs; Prediction from a Miniscale Dissolution Test and a Physiologically-Based Computer Simulation

Takano¹,

Furumoto²,

Shiraki³

et al. 2008

Pharm Res

142

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“…It would be of interest to estimate the magnitude of difference between the predictions of F in rats after oral administration using either P , or Peff for calculation. This was carried out by (8) Assuming a distended intestine, Q F= 1 --2.rRLP/Q where P represents P,,, or Peff.…”

Section: Resultsmentioning

confidence: 99%

Effect of ‘unstirred’ water layer in the intestine on the rate and extent of absorption after oral administration

Chiou

1994

Biopharm & Drug Disp

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The presence of an aqueous diffusion layer or 'unstirred' water layer adjacent to the intestinal membrane has long been regarded as a potential barrier for intestinal absorption of compounds. Theoretical analyses were performed in the present study to quantitatively determine the effect of this layer on the rate and extent of absorption of passively absorbed compounds with different membrane absorption half-lives (10 to 300 min) in humans, dogs, rabbits, rats and mice. Diffusion half-lives across this (40 microns thick) layer were estimated to be 5.8, 2.5, 1.1, 0.65 and 0.32 min, respectively, in the distended intestine of the above five species. These half-lives are reduced by about 5-fold when the intestine is about 80% 'flat' in fasting state. The results of extensive analysis indicate that the presence of such a layer is generally expected to have a relatively mild or insignificant effect on the rate of absorption and an insignificant effect on the extent of absorption. The study also indicates that an aqueous layer of 708 microns has practically no effect on the extent of absorption of progesterone, a highly lipophilic compound, in rats. For prediction of or correlation with the fraction of oral dose absorbed after oral administration, the present study indicates that use of apparent or effective permeability rather than unbiased or true wall (membrane) permeability, as advocated earlier by others, should generally suffice.

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Physiological measurements of luminal stirring in the dog and human small bowel.

Cited by 64 publications

References 27 publications

Use of maltose hydrolysis measurements to characterize the interaction between the aqueous diffusion barrier and the epithelium in the rat jejunum.

Use of maltose hydrolysis measurements to characterize the interaction between the aqueous diffusion barrier and the epithelium in the rat jejunum.

Rate-Limiting Steps of Oral Absorption for Poorly Water-Soluble Drugs in Dogs; Prediction from a Miniscale Dissolution Test and a Physiologically-Based Computer Simulation

Effect of ‘unstirred’ water layer in the intestine on the rate and extent of absorption after oral administration

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