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Antimicrobial Agents and Chemotherapy, December 2004, p. 4582-4588, Vol. 48, No. 12
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.12.4582-4588.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Effect of Sucralfate on Antibiotic Therapy for Helicobacter pylori Infection in Mice

Koichiro Watanabe,^1* Kazunari Murakami,¹ Ryugo Sato,¹ Koji Kashimura,² Masahiro Miura,³ Satoshi Ootsu,¹ Hajime Miyajima,¹ Masaru Nasu,¹ Tadayoshi Okimoto,⁴ Masaaki Kodama,⁴ and Toshio Fujioka⁴

Departments of Infectious Diseases,¹ Anatomy, Biology and Medicine,³ General Medicine, Faculty of Medicine, Oita University, Oita,⁴ Product Research Laboratory, Chugai Pharmaceutical Co., Tokyo, Japan²

Received 28 April 2004/ Returned for modification 26 July 2004/ Accepted 29 August 2004

It has been documented that sucralfate, a basic aluminum salt, enhances the efficacies of antibiotics against Helicobacter pylori, resulting in eradication rates comparable to those associated with the use of proton pump inhibitors. However, its mechanism of action remains unclear. The aim of the present study was to investigate sucralfate's ability to complement antibiotic treatment of H. pylori infection in vivo. Four weeks following induced H. pylori infection, clarithromycin (CAM) and amoxicillin (AMPC) were administered orally to C57BL/6 mice for 5 days, both with and without sucralfate or lansoprazole. When sucralfate was concurrently given with CAM and AMPC at the maximum noninhibitory doses for the treatment of H. pylori infection, the bacterial clearance rates were comparable to those achieved by treatment with lansoprazole plus those antibiotics. The results of pharmacokinetic studies showed that lansoprazole delayed gastric clearance and accelerated the absorption of CAM, whereas sucralfate suppressed both gastric clearance and absorption. AMPC was undetectable in all samples. Scanning electron microscopy with a microscope to which a energy dispersive spectrometer was attached revealed that aluminum-containing aggregated substances coated the mucosa surrounding H. pylori in mice receiving sucralfate plus antibiotics, whereas the gastric surface and pits where H. pylori had attached were clearly visible in mice receiving lansoprazole plus antibiotics. The addition of sucralfate to the antibiotic suspension resulted in a more viscous mixture that bound to the H. pylori-infected mucosa and that inhibited the loss of CAM bioavailability in the acidic environment. Sucralfate delays gastric clearance of CAM and physically captures H. pylori through the creation of an adherent mucus, which leads to bacterial clearance.

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* Corresponding author. Mailing address: Department of Infectious Diseases, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Oita 879-5593, Japan. Phone: 81(97) 586-5804. Fax: 81(97) 549-4245. E-mail: kwata{at}med.oita-u.ac.jp.

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Antimicrobial Agents and Chemotherapy, December 2004, p. 4582-4588, Vol. 48, No. 12
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.12.4582-4588.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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