IBS IBS. irritable bowel syndrome IBS IBS. in situ. E -hydroxy-l-tryptophan. -dihydroxy- -hexadien IBS IBS IBS IBS.

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1 Folia Pharmacol. Jpn.119 IBS IBS in situ E -hydroxy-l-tryptophan IBS yuji.iwanaga@abbott.com IBS 1. irritable bowel syndromeibs -dihydroxy- -hexadien IBS IBS IBS 2. 1

2 Chemical structure of polycarbophil cal- Fig. 1 cium in vitro ph. Ca in vitro ph Fig. 3 Effect of polycarbophil and CMC-Na on water flux by in situ single pass perfusion method. P.. Reproduced with permission from ref.. Pharm Sci Fig. 2 Effect of ph on equilibrium swelling of polycarbophil. Reproduced with permission from ref.. ph ph ph CMC-Na 2 in situ in situ

3 Fig. 4 Effects of loperamidea, polycarbophil calciumb, CMC-NaCand trimebutine maleatedon sennoside-induced diarrhea in dogs. P.. Reproduced with permission from ref.. E -hydroxy-l-tryptophan CMC- Na

4 Table 1 Final global improvement ratings associated with disease statusdiarrheaconstipation Status Dose Total Improvement rate L. Diarrhea M. H. Htest Cochran-Armitage test Multiple comparison More than improved P. L:M P. L:H P. M:H P. P. L. Constipation M H P. L:M P. L:H P. M:H P. P. Dose: L,. gday; M,. gday; H. gday. : Number of remarkably improved cases, :Numberof improved cases, : Number of slightly improved cases, : Number of unchanged cases, : Number of aggravated cases. means statistically significancep.. statistic significance level in multiple comparisonu test: P.. Modified from ref.. IBS 3. C C C C C 4. II IBS.g.g

5 .g.g..g..g..g.g III IBS g.g IBS -HT -HT -HT IBS -HT IBS IBS Thompson WG, Longstreth G, Drossman DA, Heaton K, Irvine EJ and Muller-Lissner S: C. Functional bowel disorders and D. Functional abdominal pain. In The Functional Gastrointestinal Disorders, Second Edition, Edited by Drossman DA, Corazziari E, Talley NJ, Thompson WG and Whitehead WE, pp -, Degnon Associates, MacLean Camilleri M and Choi MG: Review article: irritable bowel syndrome. Aliment Pharmacol Ther 11, - Camilleri M: Management of the irritable bowel syndrome. Gastroenterology 120,- Drossman D and Camilleri M: Irritable bowel syndrome: a technical review for practice guideline development. Gastroenterology 112,- IBS G IRes75,- IBS GIRes75,- Olden KW and Schuster MM: Irritable bowel syndrome. In Sleisenger Fordtran s Gastrointestinal and Liver Disease, PathophysiologyDiagnosis Management, Edited by Feldman M, Scharschmidt BF and Sleisenger MH, Vol 1, pp-, W.B. SAUNDERS COMPANY, Philadelphia Yamada T, Kitayama M, Yamazaki M, Nagata O, Tamai I and Tsuji A: Physicochemical properties of calcium polycarbophil, a water-absorbing polymer. J Pharm Pharmacol 48,- Yamada T, Saito T, Takahara E, Nagata O, Tamai I and Tsuji A: Decalcification of calcium polycarbophil in rats. Biol Pharm Bull 203,- Yamada T, Saito T, Iwanaga Y, Kitayama M, Nagata O, Tamai I and Tsuji A: The effect of polycarbophil on water transport in rat intestine. Pharm Sci 2,- Iwanaga Y, Terasaki T, Tamai I, Yamazaki M, Kato H, Ito Y, Tsuji A and Itoh Z: Effects of polycarbophil on intestinal water flux and defecation. Gastroenterology 1024, Suppl, A Yasumori A, Saito T, Kasakawa E, Mizutani F, Iwanaga Y, Morikawa K, Nagata O and Kato H: Effect of HSR-on intestinal transit in mice and rats. Jpn J Pharmacol 76, Suppl,P Saito T, Yamada T, Iwanaga Y, Morikawa K, Nagata O, Kato H, Mizumoto A and Itoh Z: Calcium polycarbophil, a water absorbing polymer, increases bowel movement and prevents sennosideinduced diarrhea in dogs. Jpn J Pharmacol 83,- Saito T, Yasumori A, Kasakawa E, Mizutani F, Iwanaga Y, Morikawa K, Nagata O and Kato H: A novel constipation model induced by low-fiber diets and the effect of HSR-in rats. Jpn J Pharmacol 76, Suppl,P Polycarbophil calciumhsr- 281,- Naggar VFB and Samaha MW: Adsorption studies of metoclopramide HCl on polycarbophil and preparation of directly compressed zero-order release tablets. Pharm Ind 515,- Polycarbophil calciumhsr- 281,- 316, -

6 HSR- II 26 Suppl, - HSR- III 26 Suppl,- Gershon MD: Review article: roles played by - hydroxytryptamine in the physiology of the bowel. Aliment Pharmacol Ther 13, Suppl,- Eglen RM and Hegde SS:-Hydroxytryptamine- HT receptors: physiology, pharmacology and therapeutic potential. Exp Opin Invest Drugs 54, - Horton R: Lotronex and the FDA: a fetal erosion of integrity. Lancet 357,- Prather CM, Camilleri M, Zinsmeister AR, McKinzie S and Thomforde G: Tegaserod accelerates orocecal transit in patients with constipationpredominant irritable bowel syndrome. Gastroenterology 118,- De Ponti F and Tonini M: Irritable bowel syndrome, New agents targeting serotonin receptor subtypes. Drugs 613,- AbstractPhysicochemical and pharmacological characteristic and clinical efficacy of an anti-irritable bowel syndrome agent, polycarbophil calciumpolyful. Yuji IWANAGALaboratory of Pharmacology, Research Division, Hokuriku Seiyaku Co., Ltd.,--Inokuchi, Katsuyama City, Fukui-, Japan. Folia Pharmacol. Jpn.Nippon Yakurigaku Zasshi119, Irritable bowel syndromeibsis a functional bowel disorder characterized by abdominal pain or discomfort and abnormal defecation. Polycarbophil calcium, a water-absorbing polymer, is expected to improve stool consistency. Polycarbophil calcium decalcified under the acidic condition and then absorbed times its weight of water under the neutral condition. In in situ experiments using rat jejunum and colon, polycarbophil decreased water absorption by the intestine without affecting water secretion. Polycarbophil inhibited prostaglandin E -,-hydroxy-l-tryptophan- and castor oil-induced diarrhea in mice or rats. Polycarbophil calcium also inhibited sennoside-induced diarrhea in dogs. Polycarbophil increased the weight of feces in naive or low-fiber diet feeding rats. In naive dogs, polycarbophil calcium increased stool frequency, stool weight and moisture. Polycarbophil was not absorbed from the gastrointestine, not metabolized and eliminated into feces in rats and dogs. Polycarbophil calcium did not affect the absorption of coadministered drugs in dogs. In the dose-finding clinical study for IBS, polycarbophil calcium was effective both in diarrhea and constipation. In the Phase III study, polycarbophil calcium was superior to trimebutine maleate in efficacy and equal in safety. Emesisvomiting and thirst were observed, but episodes of diarrhea or constipation by excessive action were few. Polycarbophil calcium seems promising as an anti- IBS agent. Keywords: irritable bowel syndrome; diarrhea; constipation; polycarbophil calcium; water-absorbing polymer Mayo Clinic Sydney F. Phillips

Diagnosis and Treatment of Irritable Bowel Syndrome

Special Issue Diagnosis and Treatment of Irritable Bowel Syndrome Myung Gyu Choi, M.D. Department of Internal Medicine The Catholic University of Korea, College of Medicine Kangnam St. Mary's Hospital