Effect of plaunotol in combination with clarithromycin or amoxicillin on Helicobacter pylori in vitro and in vivo.
Plaunotol, a cytoprotective anti-ulcer agent, has antibacterial activity against Helicobacter pylori. The purpose of the present study was to investigate the effect of plaunotol when combined with clarithromycin or amoxicillin against H. pylori. When combined with clarithromycin, plaunotol showed synergic activity against 11 of 14 strains, and additive activity against the other three strains, by chequerboard titration. When combined with amoxicillin, plaunotol showed additive activity against 10 of 14 strains. No antagonistic effects were seen against any of the strains tested. The interactions between plaunotol and either clarithromycin or amoxicillin were determined by time-kill assay against the Sydney Strain (strain SS1) of H. pylori. The combination of plaunotol with clarithromycin showed synergic activity and with amoxicillin showed additive activity. In a C57BL/6 mouse gastritis model infected with H. pylori SS1, the plaunotol-clarithromycin and plaunotol-amoxicillin combinations both exhibited synergic effects, which allowed the effective dose of clarithromycin to be reduced when co-administered with plaunotol. These results suggest that plaunotol may have a useful role in combination with anti-H. pylori drugs in the treatment of H. pylori-associated diseases.
Koga
Tetsufumi
T
Biological Research Laboratories, Sankyo Co., Ltd, 2-58 Hiromachi 1-chome, Shinagawa-ku, Tokyo 140-8710, Japan. tekoga@shina.sankyo.co.jp
Inoue
Harumi
H
Ishii
Chika
C
Okazaki
Yoko
Y
Domon
Haruki
H
Utsui
Yukio
Y
D000658:Amoxicillin / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017291:Clarithromycin / Q000494:pharmacology* / Q000627:therapeutic use; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004224:Diterpenes; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005233:Fatty Alcohols / Q000494:pharmacology* / Q000627:therapeutic use; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects* / Q000302:isolation & purification; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D013270:Stomach / Q000187:drug effects / Q000382:microbiology
D000900:Anti-Bacterial Agents; D004224:Diterpenes; D005233:Fatty Alcohols; D000658:Amoxicillin; D017291:Clarithromycin; C047686:plaunotol