Лоперамида гидрохлорид: механизм действия и возможности использования в гастроэнтерологии (обзор литературы)

1. МакНелли П.Р. Секреты гастроэнтерологии. М.: Бином, 1999. / MakNelli P.R. Sekrety gastroenterologii. M.: Binom, 1999. [in Russian]
2. Abigerges D, Armand JP, Chabot GG et al. Irinotecan (CPT-11) high-dose escalation using intensive high-dose loperamide to control diarrhea. J Natl Cancer Inst 1994; 86: 446–9.
3. American College of Gastroenterology Functional Gastrointestinal Disorders Task Force. Evidence-based position statement on the management of irritable bowel syndrome in North America. Am J Gastroenterol 2002; 97: S1–S5.
4. American Gastroenterological Association. American Gastroenterological Association medical position statement: irritable bowel syndrome. Gastroenterology 2002; 123: 2105–7.
5. American Society of Health-System Pharmacists. 56: 08 Antidiarrhea Agents. AHFS Drug Information 2007. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2007; p. 2913–8.
6. Amery W, Duyck F, Peek J, Van Den Bouwhuysen G. A multicentre double-bind study in acute diarrhoea comparing loperamide (R18553) with two common antidiarhoeal agents and a placebo. Curr Ther Res 1975; 17 (3): 263.
7. Awouters F, Megens A, Verlinden M et al. Loperamide. Survey of studies on mechanism of its anti-diarhoeal activity. Dig Dis Sci 1993; 38: 977.
8. Benson AB III, Ajani JA, Catalano RB et al. Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol 2004; 22: 2918–26.
9. Bergman L, Djarv L. A comparative study of loperamide and diphenoxylate in the treatment of chronic diarrhoea caused by intestinal resection. Ann Clin Res 1981; 13: 402–5.
10 Binnie IS, Clarke GHR, Cumberbatch JB et al. Multicentre general practice comparison of loperamide and diphenoxylate with atropine in the treatment of acute diarrhoea in adults. Br J Clin Pract 1979; 33 (3): 77.
11. Bohn LM, Raehal KM. Opioid receptor signaling: relevance for gastrointestinal therapy. Curr Opin Pharmacol 2006; 6: 559–63.
12. Bohr J, Tysk C, Eriksson S et al. Collagenous colitis: a retrospective study of clinical presentation and treatment in 163 patients. Gut 1996; 39: 846–51.
13. Burks TF, Hirning LD, Galligan JJ, Davis TP. Motility effects of opioid peptides in dog intestine. Life Sci 1982; 31: 2237–40.
14. Cann PA, Read NW, Holdsworth CD, Barends D. Role of loperamide and placebo in management of irritable bowel syndrome (IBS). Dig Dis Sci 1984; 29: 239–47.
15. Cascinu S, Bichisao E, Amadori D et al. High-dose loperamide in the treatment of 5-fluorouracil-induced diarrhea in colorectal cancer patients. Sup Care Cancer 2000; 8: 65–7.
16. Chang EB, Brown DR, Wang NS, Field M. Secretagogue-induced changes in membrane calcium permeability in chicken and chinchilla. J Clin Invest 1986; 78: 281.
17. Cummins CL, Jacobsen W, Benet LZ. Unmasking the dynamic interplay between intestinal P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 2002; 300: 1036–45.
18. De Coster M, Kerremans R, Beckers J. A comparative double-blind study of two antidiarrhoeals, difenoxine and loperamide. Tijdschr Gastroenterol 1972; 15: 337–42.
19. DeHaven-Hudkins DL, Burgos LC, Cassel JA et al. Loperamide (ADL 2-1294), an opioid antihyperalgesic agent with peripheral selectivity. J Pharmacol Exp Ther 1999; 289: 494–502.
20. Demeulenaere L, Verbeke S, Muls M, Reyntjens A. Loperamide: an open multicentre trial and double-blind cross-over comparison with placebo in patients with chronic diarrhoea. Curr Ther Res Clin Exp 1974; 16: 32–9.
21. De Luca A, Coupar IM. Insights into opioid action in the intestinal tract. Pharmacol Ther 1996; 69: 103–15.
22. Dupont HL et al. Treatment of travelers' diarrhea: randomized trial comparing rifaximin, rifaximin plus loperamide, and loperamide alone. Clin Gastroenterol Hepatol 2007; 5 (4): 451–6.
23. Efskind PS, Bernklev T, Vatn MH. A double-blind placebo-controlled trial with loperamide in irritable bowel syndrome. Scand J Gastroenterol 1996; 31: 463–8.
24. Epple HJ, Fromm M, Riecken EO, Schulzke JD. Antisecretory effect of loperamide in colon epithelial cells by inhibition of basolateral K+ conductance. Scand J Gastroenterol 2001; 36: 731–7.
25. Ericsson CD, DuPont HL, Mathewson JJ et al. Treatment of traveler's diarrhea with sulfamethoxazole and trimethoprim and loperamide. JAMA 1990; 263 (2): 257–61.
26. Ericsson CD, DuPont HL, Okhuysen PC et al. Loperamide plus azithromycin more effectively treats travelers‘ diarrhea in Mexico than azithromycin alone. J Travel Med 2007; 14 (5): 312–9.
27. Fausa O, Foerster A, Hovig T. Collagenous colitis: a clinical, histological, and ultrastructural study. Scand J Gastroenterol Suppl 1985; 107: 8–23.
28. Fox M, Stutz B, Menne D et al. The effects of loperamide on continence problems and anorectal function in obese subjects taking orlistat. Dig Dis Sci 2005; 50: 1576–83.
29. Geller RB, Gilmore CE, Dix SP et al. Randomized trial of loperamide versus dose escalation of octreotide acetate for chemotherapy-induced diarrhea in bone marrow transplant and leukemia patients. Am J Hematol 1995; 50: 167–72.
30. Göke M, Ewe K, Donner K, Meyer zum Büschenfelde KH. Influence of loperamide and loperamide oxide on the anal sphincter: a manometric study. Dis Colon Rectum 1992; 35: 857–61.
31. Hallgren T, Fasth S, Delbro DS et al. Loperamide improves anal sphincter function and continence after restorative proctocolectomy. Dig Dis Sci 1994; 39: 2612–8.
32. Heel RC, Brogden RN, Speight TM, Avery GS. Loperamide: a review of its pharmacological properties and therapeutic efficacy in diarrhoea. Drugs 1978; 15: 33–52.
33. Heykants J, Michiels M, Knaeps A, Brugmans J. Loperamide (R 18 553), a novel type of antidiarrheal agent, part 5: the pharmacokinetics of loperamide in rats and man. Arzneimittelforschung 1974; 24: 1649–53.
34. Hopman WP, Rosenbusch G, Jansen JB, Lamers CB. Effect of increasing oral doses of loperamide on gallbladder motility in man. Br J Clin Pharmacol 1990; 29: 55–60.
35. Hovdenak N. Loperamide treatment of the irritable bowel syndrome. Scand J Gastroenterol Suppl 1987; 130: 81–4.
36. Hughes S, Higgs NB, Turnberg LA. Loperamide has antisecretory activity in the human jejunum in vivo. Gut 1984; 25: 931–5.
37. John G. Symptomatic treatment of acute self-limiting diarrhoea in adults. The Practitioner 1977; 1311 (219): 396.
38. Johnson PC, Ericsson CD, DuPont HL et al. Comparison of loperamide with bismuth subsalicylate for the treatment of acute travelers' diarrhea. JAMA 1986; 255 (6): 757.
39. Jones J, Boorman J, Cann P et al. British Society of Gastroenterology guidelines for the management of the irritable bowel syndrome. Gut 2000; 47 (Suppl. 2): ii1–ii19.
40. Karim SM, Adaikan PG. The effect of loperamide on prostaglandin induced diarrhoea in rat and man. Prostaglandins 1977; 13: 321–31.
41. Keeling WF, Harris A, Martin BJ. Loperamide abolishes exercise-induced orocecal liquid transit acceleration. Dig Dis Sci 1993; 38: 1783–7.
42. Kenakin TP, Beek D. A comparison of loperamide to four calcium channel inhibitors on isolated tissues: loperamide as a calcium channel blocker. The Pharmacologist 1982; 24: 193.
43. Kim KA, Chung J, Jung DH, Park JY. Identification of cytochrome P450 isoforms involved in the metabolism of loperamide in human liver microsomes. Eur J Clin Pharmacol 2004; 60: 575–81.
44. King RFGJ, Hill GH. Effect of loperomide and codeinephosphate on ileostomy output. Clin Res Rev 1981; 1 (Suppl. 1): 207–13.
45. Lambert-Zechovsky N, Cézard JP et al. Effect of loperamide on faecal flora in infants with severe protracted diarrhoea. In: Acute infectious diarrhoea; Role of drug therapy. H.L. DuPont, 1987. Proceedings of an International Symposium held at the IX International Congress of Infectious and Parasitic diseases, Munich, 21 July, 1986.
46. Lavö B, Stenstam M, Nielsen AL. Loperamide in treatment of irritable bowel syndrome: a double-blind placebo controlled study. Scand J Gastroenterol Suppl 1987; 130: 77–80.
47. Loeschke K, Scmid Т, Farack UM. Inhibition by loperamide of mucus secretion in the rat colon in vivo. Eur J Pharmacol 1989; 170: 41.
48. Mackerer CR, Clay GA, Dajani EZ. Loperamide binding to opiate receptor sites of brain and myenteric plexus. J Pharmacol Exp Ther 1976; 199: 131–40.
49. McKay DM, Perdue MH. Intestinal epithelial function: the case for immunophysiological regulation. Cells and mediators (first of two parts). Dig Dis Sci 1993; 38 (8): 1377.
50. Merritt JE, Brown BL, Tomlinson S. Loperamide and calmodulin. Lancet 1982; 1: 283.
51. Meuris B. Observational Study of Travelers’ Diarrhea J. Travel Med 1995; 2: ll–15.
52. Nightingale J, Woodward JM. Small Bowel and Nutrition Committee of the British Society of Gastroenterology. Guidelines for management of patients with a short bowel. Gut 2006; 55 (Suppl. 4): iv1–12. 
53. Okhuysen PC, Ericsson CD. Travelers' diarrhea. Prevention and treatment. Med Clin N Am 1992; 78 (6): 1357.
54. Olesen M, Eriksson S, Bohr J et al. Lymphocytic colitis: a retrospective clinical study of 199 Swedish patients. Gut 2004; 53: 536–41.
55. Otto B, Mawe GM, Riepl RL. mu-Opiate receptor agonist loperamide blocks bethanechol-induced gallbladder contraction, despite higher cholecystokinin plasma levels in man. Neurogastroenterol Motil 2005; 17: 761–6.
56. Paterson WG, Thompson WG, Vanner SJ et al. Recommendations for the management of irritable bowel syndrome in family practice. IBS Consensus Conference Participants. Can Med Assoc J 1999; 161: 154–60.
57. Press AG, Ewe K, Schmidt J, Junge H. Effect of loperamide on jejunal electrolyte and water transport, prostaglandin E2-induced secretion and intestinal transit time in man. Eur J Clin Pharmacol 1991; 41: 239–43.
58. Quick JM. A study to compare the time taken for Arret (loperamide hydrochloride 2mg capsules) and kaolin and morphine mixture B.P.C. to control acute diarrhoea in patients presenting to the pharmacy. Janssen, U.K. dinical resarch report 1990; ARR102: 1–8.
59. Rachlis A, Gill J, Baril JG et al. Effectiveness of step-wise intervention plan for managing nelfinavir-associated diarrhea: a pilot study. HIV Clin Trials 2005; 6: 203–12.
60. Rattan S, Culver PJ. Influence of loperamide on the internal anal sphincter in the opossum. Gastroenterology 1987; 93: 121–8.
61. Read M, Read NW, Barber DC, Duthie HL. Effects of loperamide on anal sphincter function in patients complaining of chronic diarrhea with fecal incontinence and urgency. Dig Dis Sci 1982; 27: 807–14.
62. Ruoff HJ, Fladung B, Demol P, Weihrauch TR. Gastrointestinal receptors and drugs in motility disorders. Digestion 1991; 48: 1–17.
63. Schinkel AH, Wagenaar E, Mol CA, van Deemter L. P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs. J Clin Invest 1996; 97: 2517–24.
64. Stephen A, Wiggins HS, Cummings J. Effect of changing transit time on colonic microbial metabolism in man. Gut 1987; 28: 601.
65. Steffen R, Heusser R, Tschopp A, DuPont HL. Efficacy and side-effects of six agents in the self- treatment of travellers' diarrhoea. Trav Med Int 1988; 153.
66. Thompson WG, Hungin AP, Neri M et al. The management of irritable bowel syndrome: a European, primary and secondary care collaboration. Eur J Gastroenterol Hepatol 2001; 13: 933–9.
67. Tytgat GN, Huibregtse K. Loperamide and ileostomy output: placebo-controlled double-blind crossover study. Br Med J 1975; 2: 667.
68. Tytgat GN, Huibregtse K, Dagevos J, van den Ende A. Effect of loperamide on fecal output and composition in wellestablished ileostomy and ileorectal anastomosis. Am J Dig Dis 1977; 22 (8): 669–76.
69. Van Nueten JM, Janssen PA, Fontaine J. Loperamide (R 18 553), a novel type of antidiarrheal agent, part 3: in vitro studies on the peristaltic reflex and other experiments on isolated tissues. Arzneimittelforschung 1974; 24: 1641–5.
70. Varhaeren EHC, Dreessen MJ, Lemli J.A. Influence of 1,8-dihydroxyanthraquinone and loperamide on the paracelular permeability across colonic mucosa. J Pharm Pharmacol 1981; 33: 526.
71. Whitehead WE, Wald A, Norton NJ. Treatment options for fecal incontinence. Dis Colon Rectum 2001; 44: 131–42.
72. World Gastroenterology Organisation practice guideline: Acute diarrhea, March 2008.

________________________________________________

1. MakNelli P.R. Sekrety gastroenterologii. M.: Binom, 1999. [in Russian]
2. Abigerges D, Armand JP, Chabot GG et al. Irinotecan (CPT-11) high-dose escalation using intensive high-dose loperamide to control diarrhea. J Natl Cancer Inst 1994; 86: 446–9.
3. American College of Gastroenterology Functional Gastrointestinal Disorders Task Force. Evidence-based position statement on the management of irritable bowel syndrome in North America. Am J Gastroenterol 2002; 97: S1–S5.
4. American Gastroenterological Association. American Gastroenterological Association medical position statement: irritable bowel syndrome. Gastroenterology 2002; 123: 2105–7.
5. American Society of Health-System Pharmacists. 56: 08 Antidiarrhea Agents. AHFS Drug Information 2007. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2007; p. 2913–8.
6. Amery W, Duyck F, Peek J, Van Den Bouwhuysen G. A multicentre double-bind study in acute diarrhoea comparing loperamide (R18553) with two common antidiarhoeal agents and a placebo. Curr Ther Res 1975; 17 (3): 263.
7. Awouters F, Megens A, Verlinden M et al. Loperamide. Survey of studies on mechanism of its anti-diarhoeal activity. Dig Dis Sci 1993; 38: 977.
8. Benson AB III, Ajani JA, Catalano RB et al. Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol 2004; 22: 2918–26.
9. Bergman L, Djarv L. A comparative study of loperamide and diphenoxylate in the treatment of chronic diarrhoea caused by intestinal resection. Ann Clin Res 1981; 13: 402–5.
10 Binnie IS, Clarke GHR, Cumberbatch JB et al. Multicentre general practice comparison of loperamide and diphenoxylate with atropine in the treatment of acute diarrhoea in adults. Br J Clin Pract 1979; 33 (3): 77.
11. Bohn LM, Raehal KM. Opioid receptor signaling: relevance for gastrointestinal therapy. Curr Opin Pharmacol 2006; 6: 559–63.
12. Bohr J, Tysk C, Eriksson S et al. Collagenous colitis: a retrospective study of clinical presentation and treatment in 163 patients. Gut 1996; 39: 846–51.
13. Burks TF, Hirning LD, Galligan JJ, Davis TP. Motility effects of opioid peptides in dog intestine. Life Sci 1982; 31: 2237–40.
14. Cann PA, Read NW, Holdsworth CD, Barends D. Role of loperamide and placebo in management of irritable bowel syndrome (IBS). Dig Dis Sci 1984; 29: 239–47.
15. Cascinu S, Bichisao E, Amadori D et al. High-dose loperamide in the treatment of 5-fluorouracil-induced diarrhea in colorectal cancer patients. Sup Care Cancer 2000; 8: 65–7.
16. Chang EB, Brown DR, Wang NS, Field M. Secretagogue-induced changes in membrane calcium permeability in chicken and chinchilla. J Clin Invest 1986; 78: 281.
17. Cummins CL, Jacobsen W, Benet LZ. Unmasking the dynamic interplay between intestinal P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 2002; 300: 1036–45.
18. De Coster M, Kerremans R, Beckers J. A comparative double-blind study of two antidiarrhoeals, difenoxine and loperamide. Tijdschr Gastroenterol 1972; 15: 337–42.
19. DeHaven-Hudkins DL, Burgos LC, Cassel JA et al. Loperamide (ADL 2-1294), an opioid antihyperalgesic agent with peripheral selectivity. J Pharmacol Exp Ther 1999; 289: 494–502.
20. Demeulenaere L, Verbeke S, Muls M, Reyntjens A. Loperamide: an open multicentre trial and double-blind cross-over comparison with placebo in patients with chronic diarrhoea. Curr Ther Res Clin Exp 1974; 16: 32–9.
21. De Luca A, Coupar IM. Insights into opioid action in the intestinal tract. Pharmacol Ther 1996; 69: 103–15.
22. Dupont HL et al. Treatment of travelers' diarrhea: randomized trial comparing rifaximin, rifaximin plus loperamide, and loperamide alone. Clin Gastroenterol Hepatol 2007; 5 (4): 451–6.
23. Efskind PS, Bernklev T, Vatn MH. A double-blind placebo-controlled trial with loperamide in irritable bowel syndrome. Scand J Gastroenterol 1996; 31: 463–8.
24. Epple HJ, Fromm M, Riecken EO, Schulzke JD. Antisecretory effect of loperamide in colon epithelial cells by inhibition of basolateral K+ conductance. Scand J Gastroenterol 2001; 36: 731–7.
25. Ericsson CD, DuPont HL, Mathewson JJ et al. Treatment of traveler's diarrhea with sulfamethoxazole and trimethoprim and loperamide. JAMA 1990; 263 (2): 257–61.
26. Ericsson CD, DuPont HL, Okhuysen PC et al. Loperamide plus azithromycin more effectively treats travelers‘ diarrhea in Mexico than azithromycin alone. J Travel Med 2007; 14 (5): 312–9.
27. Fausa O, Foerster A, Hovig T. Collagenous colitis: a clinical, histological, and ultrastructural study. Scand J Gastroenterol Suppl 1985; 107: 8–23.
28. Fox M, Stutz B, Menne D et al. The effects of loperamide on continence problems and anorectal function in obese subjects taking orlistat. Dig Dis Sci 2005; 50: 1576–83.
29. Geller RB, Gilmore CE, Dix SP et al. Randomized trial of loperamide versus dose escalation of octreotide acetate for chemotherapy-induced diarrhea in bone marrow transplant and leukemia patients. Am J Hematol 1995; 50: 167–72.
30. Göke M, Ewe K, Donner K, Meyer zum Büschenfelde KH. Influence of loperamide and loperamide oxide on the anal sphincter: a manometric study. Dis Colon Rectum 1992; 35: 857–61.
31. Hallgren T, Fasth S, Delbro DS et al. Loperamide improves anal sphincter function and continence after restorative proctocolectomy. Dig Dis Sci 1994; 39: 2612–8.
32. Heel RC, Brogden RN, Speight TM, Avery GS. Loperamide: a review of its pharmacological properties and therapeutic efficacy in diarrhoea. Drugs 1978; 15: 33–52.
33. Heykants J, Michiels M, Knaeps A, Brugmans J. Loperamide (R 18 553), a novel type of antidiarrheal agent, part 5: the pharmacokinetics of loperamide in rats and man. Arzneimittelforschung 1974; 24: 1649–53.
34. Hopman WP, Rosenbusch G, Jansen JB, Lamers CB. Effect of increasing oral doses of loperamide on gallbladder motility in man. Br J Clin Pharmacol 1990; 29: 55–60.
35. Hovdenak N. Loperamide treatment of the irritable bowel syndrome. Scand J Gastroenterol Suppl 1987; 130: 81–4.
36. Hughes S, Higgs NB, Turnberg LA. Loperamide has antisecretory activity in the human jejunum in vivo. Gut 1984; 25: 931–5.
37. John G. Symptomatic treatment of acute self-limiting diarrhoea in adults. The Practitioner 1977; 1311 (219): 396.
38. Johnson PC, Ericsson CD, DuPont HL et al. Comparison of loperamide with bismuth subsalicylate for the treatment of acute travelers' diarrhea. JAMA 1986; 255 (6): 757.
39. Jones J, Boorman J, Cann P et al. British Society of Gastroenterology guidelines for the management of the irritable bowel syndrome. Gut 2000; 47 (Suppl. 2): ii1–ii19.
40. Karim SM, Adaikan PG. The effect of loperamide on prostaglandin induced diarrhoea in rat and man. Prostaglandins 1977; 13: 321–31.
41. Keeling WF, Harris A, Martin BJ. Loperamide abolishes exercise-induced orocecal liquid transit acceleration. Dig Dis Sci 1993; 38: 1783–7.
42. Kenakin TP, Beek D. A comparison of loperamide to four calcium channel inhibitors on isolated tissues: loperamide as a calcium channel blocker. The Pharmacologist 1982; 24: 193.
43. Kim KA, Chung J, Jung DH, Park JY. Identification of cytochrome P450 isoforms involved in the metabolism of loperamide in human liver microsomes. Eur J Clin Pharmacol 2004; 60: 575–81.
44. King RFGJ, Hill GH. Effect of loperomide and codeinephosphate on ileostomy output. Clin Res Rev 1981; 1 (Suppl. 1): 207–13.
45. Lambert-Zechovsky N, Cézard JP et al. Effect of loperamide on faecal flora in infants with severe protracted diarrhoea. In: Acute infectious diarrhoea; Role of drug therapy. H.L. DuPont, 1987. Proceedings of an International Symposium held at the IX International Congress of Infectious and Parasitic diseases, Munich, 21 July, 1986.
46. Lavö B, Stenstam M, Nielsen AL. Loperamide in treatment of irritable bowel syndrome: a double-blind placebo controlled study. Scand J Gastroenterol Suppl 1987; 130: 77–80.
47. Loeschke K, Scmid Т, Farack UM. Inhibition by loperamide of mucus secretion in the rat colon in vivo. Eur J Pharmacol 1989; 170: 41.
48. Mackerer CR, Clay GA, Dajani EZ. Loperamide binding to opiate receptor sites of brain and myenteric plexus. J Pharmacol Exp Ther 1976; 199: 131–40.
49. McKay DM, Perdue MH. Intestinal epithelial function: the case for immunophysiological regulation. Cells and mediators (first of two parts). Dig Dis Sci 1993; 38 (8): 1377.
50. Merritt JE, Brown BL, Tomlinson S. Loperamide and calmodulin. Lancet 1982; 1: 283.
51. Meuris B. Observational Study of Travelers’ Diarrhea J. Travel Med 1995; 2: ll–15.
52. Nightingale J, Woodward JM. Small Bowel and Nutrition Committee of the British Society of Gastroenterology. Guidelines for management of patients with a short bowel. Gut 2006; 55 (Suppl. 4): iv1–12. 
53. Okhuysen PC, Ericsson CD. Travelers' diarrhea. Prevention and treatment. Med Clin N Am 1992; 78 (6): 1357.
54. Olesen M, Eriksson S, Bohr J et al. Lymphocytic colitis: a retrospective clinical study of 199 Swedish patients. Gut 2004; 53: 536–41.
55. Otto B, Mawe GM, Riepl RL. mu-Opiate receptor agonist loperamide blocks bethanechol-induced gallbladder contraction, despite higher cholecystokinin plasma levels in man. Neurogastroenterol Motil 2005; 17: 761–6.
56. Paterson WG, Thompson WG, Vanner SJ et al. Recommendations for the management of irritable bowel syndrome in family practice. IBS Consensus Conference Participants. Can Med Assoc J 1999; 161: 154–60.
57. Press AG, Ewe K, Schmidt J, Junge H. Effect of loperamide on jejunal electrolyte and water transport, prostaglandin E2-induced secretion and intestinal transit time in man. Eur J Clin Pharmacol 1991; 41: 239–43.
58. Quick JM. A study to compare the time taken for Arret (loperamide hydrochloride 2mg capsules) and kaolin and morphine mixture B.P.C. to control acute diarrhoea in patients presenting to the pharmacy. Janssen, U.K. dinical resarch report 1990; ARR102: 1–8.
59. Rachlis A, Gill J, Baril JG et al. Effectiveness of step-wise intervention plan for managing nelfinavir-associated diarrhea: a pilot study. HIV Clin Trials 2005; 6: 203–12.
60. Rattan S, Culver PJ. Influence of loperamide on the internal anal sphincter in the opossum. Gastroenterology 1987; 93: 121–8.
61. Read M, Read NW, Barber DC, Duthie HL. Effects of loperamide on anal sphincter function in patients complaining of chronic diarrhea with fecal incontinence and urgency. Dig Dis Sci 1982; 27: 807–14.
62. Ruoff HJ, Fladung B, Demol P, Weihrauch TR. Gastrointestinal receptors and drugs in motility disorders. Digestion 1991; 48: 1–17.
63. Schinkel AH, Wagenaar E, Mol CA, van Deemter L. P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs. J Clin Invest 1996; 97: 2517–24.
64. Stephen A, Wiggins HS, Cummings J. Effect of changing transit time on colonic microbial metabolism in man. Gut 1987; 28: 601.
65. Steffen R, Heusser R, Tschopp A, DuPont HL. Efficacy and side-effects of six agents in the self- treatment of travellers' diarrhoea. Trav Med Int 1988; 153.
66. Thompson WG, Hungin AP, Neri M et al. The management of irritable bowel syndrome: a European, primary and secondary care collaboration. Eur J Gastroenterol Hepatol 2001; 13: 933–9.
67. Tytgat GN, Huibregtse K. Loperamide and ileostomy output: placebo-controlled double-blind crossover study. Br Med J 1975; 2: 667.
68. Tytgat GN, Huibregtse K, Dagevos J, van den Ende A. Effect of loperamide on fecal output and composition in wellestablished ileostomy and ileorectal anastomosis. Am J Dig Dis 1977; 22 (8): 669–76.
69. Van Nueten JM, Janssen PA, Fontaine J. Loperamide (R 18 553), a novel type of antidiarrheal agent, part 3: in vitro studies on the peristaltic reflex and other experiments on isolated tissues. Arzneimittelforschung 1974; 24: 1641–5.
70. Varhaeren EHC, Dreessen MJ, Lemli J.A. Influence of 1,8-dihydroxyanthraquinone and loperamide on the paracelular permeability across colonic mucosa. J Pharm Pharmacol 1981; 33: 526.
71. Whitehead WE, Wald A, Norton NJ. Treatment options for fecal incontinence. Dis Colon Rectum 2001; 44: 131–42.
72. World Gastroenterology Organisation practice guideline: Acute diarrhea, March 2008.

Л.В.Масловский*

ФГБУ ДПО Учебно-научный медицинский центр Управления делами Президента РФ. 121359, Россия, Москва, ул. Маршала Тимошенко, д. 19, стр. 1а
*unmc@yandex.ru

________________________________________________

L.V.Maslovsky*

Teaching and Research Medical Center Office of the President of the Russian Federation. 121359, Russian Federation, Moscow, ul. Marshala Timoshenko, d. 19, str. 1a
* unmc@yandex.ru