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Antimicrobial Agents and Chemotherapy, May 2002, p. 1435-1440, Vol. 46, No. 5
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.5.1435-1440.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Effects of Metronidazole, Tetracycline, and Bismuth-Metronidazole-Tetracycline Triple Therapy in the Helicobacter pylori SS1 Mouse Model after 1 Day of Dosing: Development of an H. pylori Lead Selection Model

Christine F. Sizemore ,,{dagger} Joel D. Quispe, Karen M. Amsler, Todd C. Modzelewski, Jayson J. Merrill, D. Andrew Stevenson, Lorie A. Foster, and Andrew M. Slee*

Antimicrobial Research Department, DuPont Pharmaceuticals Company, Wilmington, Delaware 19880-0400

Received 29 December 2000/ Returned for modification 4 June 2001/ Accepted 6 February 2002

We evaluated the effect of optimized doses and dosing schedules of metronidazole, tetracycline, and bismuth-metronidazole-tetracycline (BMT) triple therapy with only 1 day of dosing on Helicobacter pylori SS1 titers in a mouse model. A reduction of bacterial titers was observable with 22.5 and 112.5 mg of metronidazole per kg of body weight (as well as BMT) given twice daily and four times daily (QID). Two hundred milligrams of tetracycline per kilogram, given QID, resulted in only a slight reduction of H. pylori titers in the stomach. We argue that optimization of doses based on antimicrobial drug levels in the animal and shortened (1 or 2 days) drug administration can be used to facilitate early evaluation of putative anti-H. pylori drug candidates in lieu of using human doses and extended schedules (7 to 14 days), as can be deduced from the results seen with these antimicrobial agents.

* Corresponding author. Present address: Enanta Pharmaceuticals, Inc., 500 Arsenal St., Watertown, MA 02472. Phone: (617) 607-0800. Fax: (617) 607-0530. E-mail: aslee{at}enanta.com.

{dagger} Present address: Respiratory Diseases Branch, Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD.

Antimicrobial Agents and Chemotherapy, May 2002, p. 1435-1440, Vol. 46, No. 5
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.5.1435-1440.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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