Digestive Diseases and Sciences

, Volume 41, Issue 3, pp 543–548 | Cite as

Effect of cisapride on gallbladder emptying and plasma CCK in normal and vagotomized human subjects

  • R. Patankar
  • M. M. Ozmen
  • A. Sanderson
  • C. D. Johnson
Pancreatic And Biliary Disorders


Previous studies have provided conflicting results on the effects of cisapride on gallbladder emptying in response to a meal. We studied six volunteers and six patients after a truncal vagotomy in a double-blind, placebo-controlled, prospectively randomized study using 10 mg cisapride four times a day for three days. Gallbladder volume was quantitated using ultrasonography, and plasma CCK levels were measured with a sensitive and specific radioimmunoassay using the DINO antibody before and for 90 min after a fatty, mixed meal. Plasma CCK levels were unchanged after treatment with cisapride in both groups. No prokinetic effect was observed on the gallbladder either in normal subjects or vagotomized patients. Paradoxically, residual volume (RV) was increased in the vagotomized patients after treatment with cisapride: RV cisapride 7.1 (4.1–15.9) ml, RV placebo 5.1 (3.8–14) ml,P<0.05. Further work is required to clarify the mechanisms of action of cisapride on the gallbladder and the sphincter of Oddi. The use of cisapride during litholytic therapy may impair gallbladder emptying and delay stone clearance.

Key words

cisapride gallbladder cholecystokinin 


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  1. 1.
    Sitzmann JV, Pitt HA, Steinborn PA, Pasha ZR, Sanders RC: CCK prevents parenteral nutrition induced biliary sludge in humans. Surg Gynecol 170:25–31, 1990Google Scholar
  2. 2.
    Lee KY, Chey WY, You CH, Shah AN, Hamilton D: Effect of cisapride on the motility of gut in dogs and colonic transit time in dogs and humans. Gastroenterology 86:1157, 1984Google Scholar
  3. 3.
    Edwards CA, Holden S, Brown C, Read NW: Effect of cisapride on the gastrointestinal transit of a solid meal in normal human subjects. Gut 28:13–16, 1987Google Scholar
  4. 4.
    Schuurkes JAJ, Van Neuten JM: Animal pharmacology of the gastrointestinal prokinetic, cisapride.In Progress in the Treatment of Gastrointestinal Motility Disorders: The Role of Cisapride. AG Johnson, G Lux (eds). Amsterdam, Excerpta Medica, 1988, pp 11–18 N54025Google Scholar
  5. 5.
    Craig DA, Clarke DE: Pharmacological characterisation of a neuronal receptor for 5-hydroxytryptamine in guinea pig ileum with properties similar to the 5-HT4 receptor. J Pharmacol Exp Ther 252:1378–1386, 1990Google Scholar
  6. 6.
    Hill JM, Bunce KT, Humphrey PPA: Investigation of the neuronal non 5 HT3 receptor mediating contraction of the guinea pig ileum. Br J Pharmacol 99:182P, 1990Google Scholar
  7. 7.
    McKirdy HC, McKirdy ML, Marshall RW: Effects of cisapride on isolated muscle strips from human digestive tract. J. Physiol 422:88P, 1990Google Scholar
  8. 8.
    Marzio L, DiFelice F, Laico MG, Imbimbo B, Lapenna D, Cuccurullo F: Gallbladder hypokinesia and normal gastric emptying of liquids in patients with dyspeptic symptoms. Dig Dis Sci 37:262–267, 1992Google Scholar
  9. 9.
    Ziegenhagen DJ, Glimm E, Kruis W, Zehnter E: Oral cisapride increases gallbladder volume in volunteers. J Gastrointest Motil 4:119–123, 1992Google Scholar
  10. 10.
    Clave RA, Gaspar MA: Incidence of gallbladder disease after vagotomy. Am J Surg 118:169, 1969Google Scholar
  11. 11.
    Ihasz M, Griffith CA: Gallstones after vagotomy. Am J Surg 141:141–150, 1981Google Scholar
  12. 12.
    Parkin GJS, Smith RB, Johnston D: Gallbladder volume and contractility after truncal, selective and highly selective vagotomy in man. Ann Surg 178:581–586, 1973Google Scholar
  13. 13.
    Pechlivanides G, Xynos E, Chrysos E, et al: Gallbladder emptying after antiulcer gastric surgery. Am J Surg 168:335–339, 1994Google Scholar
  14. 14.
    Beardshall K, Deprez P, Playford RJ, Alexander M, Calam J: Effect of chymotrypsin on human CCK release: use of clostripain in the validation of a new radioimmunoassay. Regul Pept 40(1):1–12, 1992Google Scholar
  15. 15.
    Everson GT, Braverman DZ, Johnson ML, Kern F: A critical evaluation of real-time ultrasonography for the study of gallbladder volume and contraction. Gastroenterology 79:40, 1980Google Scholar
  16. 16.
    Dodds WJ, Groh WJ, Darweesh RMA, Lawson TL, Kishk SMA, Kern MK: Sonographic measurement of gallbladder volume. AJR 145:1003–1011, 1985Google Scholar
  17. 17.
    Koop H, Monnikes H, Koop I, Dionysius J, Schwarz C, Arnold R: Effect of the prokinetic drug cisapride on gastrointestinal hormone release. Scand J Gastroenterol 21:907–913, 1986Google Scholar
  18. 18.
    Hopman WPM, Kestens PJSM, DeJong AJL, Hafkensheid JC, Jansen JBMJ, Lamers CB: Effect of cisapride on gallbladder volume and pancreatic enzyme and plasma pancreatic polypeptide secretion in man. Neth J Med 29:149, 1986Google Scholar
  19. 19.
    Marzio L, DiGiammarco AM, Capone F: Effect of cisapride on human fasting gallbladder volume: A real-time ultrasonographic study. Eur J Clin Pharmacol 29:631–633, 1986Google Scholar
  20. 20.
    Marzio L, Neri M, De Angelis C, DiFelice F, Celiberti V, Pieramico O, Mezzeti A, Cuccurullo F: Effect of cisapride on gallbladder kinetics in normals and patients with decreased gallbladder response to a liquid meal. Curr Ther Res 42:895–900, 1987Google Scholar
  21. 21.
    Mambrini P, Perreard M, Gerolami A: Effects of alcohol on gallbladder emptying in response to a normal meal in healthy subjects. HPB Surg S32, 1993Google Scholar
  22. 22.
    Ziegenhagen DJ, Heitz W, Kruis W, Pohl C, Zehnter E: Cisapride increases gallbladder volume in gallstone patients before and after extracorporeal shock wave lithotripsy. Aliment Pharmacol Ther 7:617–622, 1993Google Scholar
  23. 23.
    Thorens J, Schnegg JF, Froehlich F, Jansen JB, Dorta G, Blum AL, Gonvers JJ, Fried M: Effect of cisapride on gallbladder motility after extracorporeal shock wave lithotripsy. J Hepatol 22:333–337, 1995Google Scholar
  24. 24.
    Wenzl H, Pristautz, Schreiber F, Krejs GJ: Cisapride does not improve clearance of stone fragments after extracorporeal shock wave lithotripsy for gallstones. Gastroenterology 102:A338, 1992Google Scholar
  25. 25.
    McCallum R, Chakrapani P, Campoli-Richards D, Goa K: Cisapride: A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use as a prokinetic agent in gastrointestinal motility disorders. Drugs 36:652–681, 1988Google Scholar
  26. 26.
    Baker RA, Saccone GTP, Touuli J: Cisapride inhibits motility of the sphincter of Oddi in the Australian possum. Dig Dis Sci 35:711–715, 1990Google Scholar
  27. 27.
    Liu YF, Saccone GT, Theane A, Baker RA, Harvey JK, Toouli J: Sphincter of Oddi regulates flow by acting as a variable resistor to flow. Am J Physiol 263:G683-G689, 1992Google Scholar
  28. 28.
    Nakayama S, Neya T, Yamasato T, Takaki M, Itano N: Effects of cisapride on the motility of digestive tract in dogs and guinea pigs. Jpn J Smooth Muscle Res 21:1–9, 1985Google Scholar
  29. 29.
    Takaishi O, Ozaki S, Arakawi T, Kobayashi K: Cisapride stimulates motility of isolated rabbit sphincter of Oddi through 5-HT3 receptorin vitro. Gastroenterology 102:A335, 1992Google Scholar
  30. 30.
    Takaaki J, Akaki H, Furuya S, Morita M, Hukui Y, Sato T, Hukuda S, Kodama T, Kashima K: Effect of cisapride on the motor activity of the sphincter of Oddi in humans; evaluation by endoscopic biliary manometry. J Clin Exp Med 161:483–484, 1992Google Scholar
  31. 31.
    Khalil T, Walker JP, Weiner J, Fagan CJ, Townsend CM, et al: Effect of ageing on gallbladder contraction and release of CCK 33. Surgery 98:423–429, 1985Google Scholar
  32. 32.
    Patankar R, Bailey I, Sanderson A, Johnson CD: Bile stasis after truncal vagotomy. HPB Surg 6:38, 1993Google Scholar
  33. 33.
    Patankar R, Ozmen MM, Johnson CD: Relative contribution of truncal vagotomy and pyloroplasty to raised postoperative CCK levels in man. J Physiol 47:74P, 1994Google Scholar

Copyright information

© Plenum Publishing Corporation 1996

Authors and Affiliations

  • R. Patankar
    • 1
  • M. M. Ozmen
    • 1
  • A. Sanderson
    • 1
  • C. D. Johnson
    • 1
  1. 1.From the University Surgical Unit and Department of RadiologySouthampton General HospitalSouthamptonUK

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