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.
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.
Sizemore
Christine F
CF
Antimicrobial Research Department, DuPont Pharmaceuticals Company, Wilmington, Delaware 19880-0400, USA.
Quispe
Joel D
JD
Amsler
Karen M
KM
Modzelewski
Todd C
TC
Merrill
Jayson J
JJ
Stevenson
D Andrew
DA
Foster
Lorie A
LA
Slee
Andrew M
AM
D000818:Animals; D001729:Bismuth / Q000008:administration & dosage* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D008795:Metronidazole / Q000008:administration & dosage* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000627:therapeutic use; D012459:Salicylates / Q000008:administration & dosage* / Q000627:therapeutic use; D013752:Tetracycline / Q000008:administration & dosage* / Q000627:therapeutic use
D009942:Organometallic Compounds; D012459:Salicylates; D008795:Metronidazole; C015715:bismuth subsalicylate; D013752:Tetracycline; D001729:Bismuth