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First-Pass Accumulation of Salicylic Acid in Gut Tissue After Absorption in Anesthetized Rat

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Abstract

Purpose. The purpose of this paper is to report the study on the first-pass accumulation kinetics of salicylic acid (SA) in gut tissue after absorption by simultaneously analyzing drug contents in the lumen, gut tissue, and blood in anesthetized rats.

Methods. Sodium salicylate (5.4 mg as SA) in 0.4 ml normal saline was administered into a closed 10-cm jejunal loop. Drained mesenteric blood from the loop area was collected every minute, while lost blood was replaced through infusion of oxygenated blood from donor rats. At 3, 10, 20, 40, or 60 min after dosing, SA remaining in lumen, accumulating in gut tissue, and appearing in blood were analyzed by HPLC. All the data were fitted into a linear two-consecutive (lumen and gut tissue) first-order kinetic model.

Results. After absorption, significant amounts of SA accumulated in gut tissue before appearing in blood, e.g., at 3 or 20 min after dosing, 74.4 or 54.4% of absorbed SA accumulated in gut tissue, respectively. Practically all administered SA was recovered. The estimated mean absorption time from the lumen and mean transit time in gut tissue of SA were 20.4 and 18.5 min, respectively.

Conclusions. The above results indicate that gut tissue may act as a reservoir for drug accumulation during the first pass after oral absorption. Thus, the rate of transport of drug into blood circulation after oral administration may significantly differ from the true rate of absorption through the gut membrane. The potential transport resistance from gut tissue to blood should probably be considered in the modeling of GI absorption.

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REFERENCES

  1. M. Gibaldi and D. Perrier. Pharmacokinetics. 2nd ed., Marcel Dekker, New York, 1982.

    Google Scholar 

  2. M. L. Chen and W. L. Chiou. Assessment of rate of absorption in bioequivalence studies. J. Chinese Pharm. Assoc. 44:173–184 (1992).

    Google Scholar 

  3. W. L. Chiou. The phenomenon and rationale of marked dependence of drug concentration on blood sampling site: Implication in pharmacokinetics, pharmacodynamics, toxicology and therapeutics (Part II). Clin. Pharmacokinet. 17:275–290 (1989).

    Google Scholar 

  4. W. L. Chiou. Mean hepatic transit time in the determination of mean absorption time. J. Pharm. Sci. 72:1365–1368 (1983).

    Google Scholar 

  5. Y. S. Choo. First-pass accumulation of drugs in gut wall after absorption: Mechanism and implications in absorption studies. Ph.D. Thesis, University of Illinois, Chicago, 1992.

  6. W. L. Chiou. Determination of drug permeability in a flat or distended stirred intestine—prediction of fraction dose absorbed in humans after oral administration. Int. J. Clin. Pharmacol. Ther. 32:474–482 (1994).

    Google Scholar 

  7. W. L. Chiou. We may not measure correct intestinal wall permeability coefficient of drugs: An alternative absorptive clearance concept. J. Pharmacokin. Biopharm (in press).

  8. D. Cutler. Assessment of rate and extent of drug absorption. Pharmacol. Ther. 14:123–160 (1981).

    Google Scholar 

  9. P. J. Hanson, and D. S. Parson. The utilization of glucose and production of lactate in vitro preparations of rat small intestine: Effect of vascular perfusion. J. Physiol. 255:775–795 (1976).

    Google Scholar 

  10. B. E. Cham, D. Johns, F. Bochner, D. M. Imhoff, and M. Rowland. Simultaneous liquid-chromatographic quantification of salicylic acid, salicyluric acid, and gentisic acid in plasma. Clin. Chem. 25:1420–1425 (1979).

    Google Scholar 

  11. G. W. Peng and W. L. Chiou. Analysis of drugs and other toxic substances in biological samples for pharmacokinetic studies. J. Chromat. Biomed. Appl. 531:3–50 (1990).

    Google Scholar 

  12. H. Ochsenfarhrt and D. Winne. The contribution of solvent drag to the intestinal absorption of the acidic drugs benzoic acid and salicylic acid from the jejunum of the rat. Naunyn-Schmiedeberg's Arch. Pharmacol. 281:197–217 (1974).

    Google Scholar 

  13. W. L. Chiou. Critical evaluation of the potential error in pharmacokinetic studies of using the linear trapezoidal rule method for calculation of the area under the plasma level-time curve. J. Pharmacokinet. Biochem. 6:539–546 (1978).

    Google Scholar 

  14. R. J. Sawchuck and W. M. Awni. Absorption of cyclosporine from rabbit small intestine in situ. J. Pharm. Sci. 75:1151–1155 (1986).

    Google Scholar 

  15. K. Dackson, J. A. Stone, K. J. Palin, and W. N. Charman. Evaluation of the mass assumption with respect to the two-resistance model of intestinal absorption by using in situ single-pass intestinal perfusion of theophylline in rats. J. Pharm. Sci. 81:321–325 (1992).

    Google Scholar 

  16. J. T. Doluisio, W. G. Crouthamel, G. H. Tan, J. V. Swintosky, and L. W. Dittert. Drug absorption III: Effect of membrane storage on the kinetics of drug absorption. J. Pharm. Sci. 59:72–76 (1970).

    Google Scholar 

  17. D. Winne, H. Gorig, and U. Muller. Closed rat jejunal segment in situ: Role of pre-epithelial diffusion resistance (unstirred layer) in the absorption process and model analysis. Naunyn-Schmiedeberg's Arch. Pharmacol. 335:204–215 (1987).

    Google Scholar 

  18. D. G. Mcdevitt and A. S. Nies. Simultaneous measurement of cardiac output and its distribution with microspheres in the rat. Cardiovasc. Res. 10:494–498 (1976).

    Google Scholar 

  19. G. Levy and W. J. Jusko. Effect of viscosity on drug absorption. J. Pharm. Sci. 54:219–255 (1965).

    Google Scholar 

  20. V. K. Piotrovskij, G. Paintaud, G. Alván, and T. Trnovec. Modeling of the saturable time-constrained amoxicillin absorption in humans. Pharm. Res. 11:1346–1351 (1994).

    Google Scholar 

  21. H. Gudjonsson, B. U. K. Li, A. L. Shug, and W. A. Olsen: In vivo studies of intestinal carnitine absorption in rats. Gastroenterology, 88:1880–1887 (1985).

    Google Scholar 

  22. Y. S. Choo, Y. M. Choi, and W. L. Chiou. First-pass accumulation of drugs in gut wall after absorption: mechanisms and implications in absorption studies. Pharm. Res. 9:S-3 (1992).

    Google Scholar 

  23. W. L. Chiou. Effect of ‘unstirred’ water layer in the intestine on the rate and extent of absorption after oral administration. Biopharm. & Drug Dispos. 15:709–717 (1994).

    Google Scholar 

  24. W. L. Chiou. The validation of the intestinal permeability approach to predict oral fraction of dose absorbed in humans and rats. Biopharm. & Drug Dispos. 16:71–75 (1995).

    Google Scholar 

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Authors and Affiliations

  1. Department of Pharmaceutics and Pharmacodynamics (M/C 865), College of Pharmacy, University of Illinois at Chicago, 833 South Wood St., Chicago, IL 60612, USA

    Young M. Choi, Sang M. Chung & Win L. Chiou

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  1. Young M. Choi
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  2. Sang M. Chung
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  3. Win L. Chiou
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Choi, Y.M., Chung, S.M. & Chiou, W.L. First-Pass Accumulation of Salicylic Acid in Gut Tissue After Absorption in Anesthetized Rat. Pharm Res 12, 1323–1327 (1995). https://doi.org/10.1023/A:1016273623737

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