Effect of dosing volume on gastrointestinal absorption in rats: analysis of the gastrointestinal disposition of L-glucose and estimation of in vivo intestinal membrane permeability.


:The effect of the oral dosing volume (DV) on both gastric emptying and intestinal absorption was examined by analyzing the gastrointestinal disposition of a model solute, L-glucose, in rats. The amount of 14C-labeled L-glucose in the gastric and intestinal contents of sacrificed rats was measured at various times after administration, and the data were analyzed with a linear model, assuming first-order gastric emptying followed by first-order intestinal absorption. The gastric emptying rate constant (kg) rose from 0.025 to 0.072 min-1 by increasing DV from 0.1 to 3 mL/rat, whereas the intestinal absorption rate constant (ka) decreased from 0.031 to 0.015 min-1. This decrease in ka was attributed to an increase in the average intestinal lumen volume (Vav) from 24 to 39 microL/cm, assuming that the relationship ka = CLa,app/Vav holds (where CLa,app is the apparent intestinal membrane permeability clearance or the product of the apparent membrane permeability coefficient and surface area). The CLa,app (= kaVav), a measure of the in vivo intestinal membrane permeability, was 0.74 microL/cm/min for a DV value of 0.1 mL/rat and decreased only marginally by 20% for larger values of DV, suggesting an insignificant effect of DV on CLa,app. These results suggest that the accelerating effect of the increased kg, produced by the increased DV on the gastrointestinal absorption, may be canceled by the decrease in ka. A decrease in ka may lead to a decrease in the fraction absorbed. Finally, this study also provides a means for carrying out physiological modeling of drug absorption following oral administration.


J Pharm Sci


Yuasa H,Numata W,Ozeki S,Watanabe J




Has Abstract


1995-04-01 00:00:00














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    journal_title:Journal of pharmaceutical sciences

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    authors: Graffner C,Johansson ME,Nicklasson M,Nyqvist H

    更新日期:1985-01-01 00:00:00

  • Physicochemical characterization of nedocromil bivalent metal salt hydrates. 3. Nedocromil calcium.

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    journal_title:Journal of pharmaceutical sciences

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    authors: Zhu H,Halfen JA,Young VG Jr,Padden BE,Munson EJ,Menon V,Grant DJ

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  • IgG1 adsorption to siliconized glass vials-influence of pH, ionic strength, and nonionic surfactants.

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    journal_title:Journal of pharmaceutical sciences

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    authors: Höger K,Mathes J,Frieß W

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    journal_title:Journal of pharmaceutical sciences

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    authors: Sethi ML

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  • Progesterone retention by rat uterus I. Pharmacokinetics after uterine intraluminal instillation.

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    journal_title:Journal of pharmaceutical sciences

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    更新日期:1977-12-01 00:00:00

  • Collagen/PLGA microparticle composites for local controlled delivery of gentamicin.

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    authors: Schlapp M,Friess W

    更新日期:2003-11-01 00:00:00

  • Plasma binding of benzodiazepines in humans.

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    authors: Johnson RF,Schenker S,Roberts RK,Desmond PV,Wilkinson GR

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  • Differences in Food Effects for 2 Weak Bases With Similar BCS Drug-Related Properties: What Is Happening in the Intestinal Lumen?

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    authors: Kobori T,Harada S,Nakamoto K,Tokuyama S

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  • Improving ultrasound reflectivity and stability of echogenic liposomal dispersions for use as targeted ultrasound contrast agents.

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  • Passive Immunotherapies Targeting Amyloid Beta and Tau Oligomers in Alzheimer's Disease.

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  • Dissolution rate studies of compression-molded units made from hydroxypropyl cellulose films.

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    journal_title:Journal of pharmaceutical sciences

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  • Determination of free extracellular concentrations of piperacillin by microdialysis.

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  • Prediction of xanthine solubilities using statistical techniques.

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    authors: Ochsner AB,Belloto RJ Jr,Sokoloski TD

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  • Sucrose esters increase drug penetration, but do not inhibit p-glycoprotein in caco-2 intestinal epithelial cells.

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    journal_title:Journal of pharmaceutical sciences

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  • Protection of bovine serum albumin from aggregation by Tween 80.

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    authors: Arakawa T,Kita Y

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    authors: Schieffer GW,Palermo PJ,Pollard-Walker S

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    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


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    pub_type: 杂志文章,评审


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    pub_type: 杂志文章


    authors: Mayberry DO,Kowblansky M,Lane PA,Wray PE

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    pub_type: 杂志文章,评审


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    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


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    更新日期:2003-11-01 00:00:00