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. 1992 Jul;34(1):40–46. doi: 10.1111/j.1365-2125.1992.tb04105.x

Effects of a non-absorbable osmotic load on drug absorption in healthy volunteers.

S A Riley 1, M Kim 1, F Sutcliffe 1, M Kapas 1, M Rowland 1, L A Turnberg 1
PMCID: PMC1381373  PMID: 1633066

Abstract

1. We have studied the effects of a non-absorbable osmotic load on the absorption of a multicomponent solution of frusemide, atenolol, hydrochlorothiazide and salicylic acid in six healthy volunteers. 2. Each subject was studied on up to four separate occasions. The drugs were administered in one of four solutions: a) a mannitol/electrolyte solution, b) a double-strength mannitol/electrolyte solution, c) a glucose/electrolyte solution and d) water. Lactulose or sulphasalazine were added as oro-caecal transit markers. Lactulose was included in the mannitol- and glucose-based solutions, adding a further non-absorbable osmotic load, and sulphasalazine was added to the water, adding little osmotic load. 3. The absorption of atenolol and hydrochlorothiazide was two- to three-times less from all lactulose-containing solutions than from the sulphasalazine-containing solution. The absorption of frusemide and salicylic acid was similar from all four solutions. 4. The largest non-absorbable osmotic load impaired the absorption of atenolol and hydrochlorothiazide most and the incorporation of glucose only partly restored absorption. 5. These results suggest that transmucosal water movement is an important determinant of atenolol and hydrochlorothiazide absorption but is less relevant for the absorption of frusemide and salicylic acid. Furthermore, these data demonstrate a previously unrecognised interaction between a commonly prescribed laxative--lactulose, and atenolol and hydrochlorothiazide.

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Selected References

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  1. Beermann B., Groschinsky-Grind M. Pharmacokinetics of hydrochlorothiazide in man. Eur J Clin Pharmacol. 1977 Dec 2;12(4):297–303. doi: 10.1007/BF00607430. [DOI] [PubMed] [Google Scholar]
  2. Bock O. A., Richards W. C., Witts L. J. The relationship between acid secretion after augmented histamine stimulation and the histology of the gastric mucosa. Gut. 1963 Jun;4(2):112–114. doi: 10.1136/gut.4.2.112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bond J. H., Jr, Levitt M. D., Prentiss R. Investigation of small bowel transit time in man utilizing pulmonary hydrogen (H2) measurements. J Lab Clin Med. 1975 Apr;85(4):546–555. [PubMed] [Google Scholar]
  4. Charney E. B., Bodurtha J. N. Brief clinical and laboratory observations. J Pediatr. 1981 Jan;98(1):157–158. doi: 10.1016/s0022-3476(81)80563-x. [DOI] [PubMed] [Google Scholar]
  5. DREILING D. A., JANOWITZ H. D. The secretion of electrolytes by the human pancreas; the effect of diamox, ACTH, and disease. Am J Dig Dis. 1959 Feb;4(2):127–144. doi: 10.1007/BF02231234. [DOI] [PubMed] [Google Scholar]
  6. Davis G. R., Santa Ana C. A., Morawski S. G., Fordtran J. S. Development of a lavage solution associated with minimal water and electrolyte absorption or secretion. Gastroenterology. 1980 May;78(5 Pt 1):991–995. [PubMed] [Google Scholar]
  7. Gryboski J. D. Diarrhea from dietetic candies. N Engl J Med. 1966 Sep 29;275(13):718–718. doi: 10.1056/NEJM196609292751309. [DOI] [PubMed] [Google Scholar]
  8. Haynes R. B., Sackett D. L., Gibson E. S., Taylor D. W., Hackett B. C., Roberts R. S., Johnson A. L. Improvement of medication compliance in uncontrolled hypertension. Lancet. 1976 Jun 12;1(7972):1265–1268. doi: 10.1016/s0140-6736(76)91737-2. [DOI] [PubMed] [Google Scholar]
  9. Hickey C. A., Calloway D. H., Murphy E. L. Intestinal gas production following ingestion of fruits and fruit juices. Am J Dig Dis. 1972 May;17(5):383–389. doi: 10.1007/BF02231287. [DOI] [PubMed] [Google Scholar]
  10. Holgate A. M., Read N. W. Relationship between small bowel transit time and absorption of a solid meal. Influence of metoclopramide, magnesium sulfate, and lactulose. Dig Dis Sci. 1983 Sep;28(9):812–819. doi: 10.1007/BF01296904. [DOI] [PubMed] [Google Scholar]
  11. Kellow J. E., Borody T. J., Phillips S. F., Haddad A. C., Brown M. L. Sulfapyridine appearance in plasma after salicylazosulfapyridine. Another simple measure of intestinal transit. Gastroenterology. 1986 Aug;91(2):396–400. doi: 10.1016/0016-5085(86)90574-3. [DOI] [PubMed] [Google Scholar]
  12. Kennedy M., Chinwah P., Wade D. N. A pharmacological method of measuring mouth caecal transit time in man. Br J Clin Pharmacol. 1979 Oct;8(4):372–373. doi: 10.1111/j.1365-2125.1979.tb04723.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ladas S. D., Isaacs P. E., Sladen G. E. Post-prandial changes of osmolality and electrolyte concentration in the upper jejunum of normal man. Digestion. 1983;26(4):218–223. doi: 10.1159/000198893. [DOI] [PubMed] [Google Scholar]
  14. Mason W. D., Winer N., Kochak G., Cohen I., Bell R. Kinetics and absolute bioavailability of atenolol. Clin Pharmacol Ther. 1979 Apr;25(4):408–415. doi: 10.1002/cpt1979254408. [DOI] [PubMed] [Google Scholar]
  15. Miller L. J., Malagelada J. R., Go V. L. Postprandial duodenal function in man. Gut. 1978 Aug;19(8):699–706. doi: 10.1136/gut.19.8.699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Needs C. J., Brooks P. M. Clinical pharmacokinetics of the salicylates. Clin Pharmacokinet. 1985 Mar-Apr;10(2):164–177. doi: 10.2165/00003088-198510020-00004. [DOI] [PubMed] [Google Scholar]
  17. Niemeyer C., Hasenfuss G., Wais U., Knauf H., Schäfer-Korting M., Mutschler E. Pharmacokinetics of hydrochlorothiazide in relation to renal function. Eur J Clin Pharmacol. 1983;24(5):661–665. doi: 10.1007/BF00542218. [DOI] [PubMed] [Google Scholar]
  18. Ochsenfahrt H., Winne D. 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 Schmiedebergs Arch Pharmacol. 1974;281(2):197–217. doi: 10.1007/BF00503498. [DOI] [PubMed] [Google Scholar]
  19. Ochsenfahrt H., Winne D. The contribution of solvent drag to the intestinal absorption of the basic drugs amidopyrine and antipyrine from the jejunum of the rat. Naunyn Schmiedebergs Arch Pharmacol. 1974;281(2):175–196. doi: 10.1007/BF00503497. [DOI] [PubMed] [Google Scholar]
  20. Phillips S. F. Diarrhea: a current view of the pathophysiology. Gastroenterology. 1972 Sep;63(6):495–518. [PubMed] [Google Scholar]
  21. Phillips S. F., Giller J. The contribution of the colon to electrolyte and water conservation in man. J Lab Clin Med. 1973 May;81(5):733–746. [PubMed] [Google Scholar]
  22. Ponto L. L., Schoenwald R. D. Furosemide (frusemide). A pharmacokinetic/pharmacodynamic review (Part I). Clin Pharmacokinet. 1990 May;18(5):381–408. doi: 10.2165/00003088-199018050-00004. [DOI] [PubMed] [Google Scholar]
  23. Riley S. A., Sutcliffe F., Kim M., Kapas M., Rowland M., Turnberg L. A. The influence of gastrointestinal transit on drug absorption in healthy volunteers. Br J Clin Pharmacol. 1992 Jul;34(1):32–39. doi: 10.1111/j.1365-2125.1992.tb04104.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Staniforth D. H. Comparison of orocaecal transit times assessed by the lactulose/breath hydrogen and the sulphasalazine/sulphapyridine methods. Gut. 1989 Jul;30(7):978–982. doi: 10.1136/gut.30.7.978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Turnberg L. A. The pathophysiology of diarrhoea. Clin Gastroenterol. 1979 Sep;8(3):551–568. [PubMed] [Google Scholar]
  26. Waitman A. M., Dyck W. P., Janowitz H. D. Effect of secretin and acetazolamide on the volume and electrolyte composition of hepatic bile in man. Gastroenterology. 1969 Feb;56(2):286–294. [PubMed] [Google Scholar]
  27. Waller E. S., Massarella J. W., Tomkiw M. S., Smith R. V., Doluisio J. T. Pharmacokinetics of furosemide after three different single oral doses. Biopharm Drug Dispos. 1985 Apr-Jun;6(2):109–117. doi: 10.1002/bdd.2510060202. [DOI] [PubMed] [Google Scholar]
  28. Winstanley P. A., Orme M. L. The effects of food on drug bioavailability. Br J Clin Pharmacol. 1989 Dec;28(6):621–628. doi: 10.1111/j.1365-2125.1989.tb03554.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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