The 7alpha-methoxy substituent in cephem or oxacephem antibiotics enhances in vivo anti-Helicobacter felis activity in mice after oral administration.
The in vivo antibacterial activities of 7alpha-methoxy-cephems or 7alpha-methoxy-1-oxacephems and their demethoxy congeners after oral administration were compared in a mouse model of gastric infection with Helicobacter felis. The MICs of all four pairs of compounds with and without the 7alpha-methoxy substituent were within one two-fold dilution for H. felis and Helicobacter pylori, but the 7alpha-methoxy compounds were at least four-fold more active at bacterial eradication than their demethoxy congeners. Since these compounds are not absorbed after oral administration, they are likely to have gained direct access to the bacteria from the gastric cavity. Thus the 7alpha-methoxy substituent may enhance in vivo activity by promoting the gastric mucus permeability of the compounds or by allowing the compounds to remain longer in the gastric cavity.
Kobayashi
Y
Y
Shionogi Research Laboratories, 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan. yoshinao.kobayashi@shionogi.co.jp
Doi
M
M
Nagata
H
H
Kubota
T
T
Kume
M
M
Murakami
K
K
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D016998:Helicobacter / Q000187:drug effects*; D016481:Helicobacter Infections / Q000188:drug therapy / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D013997:Time Factors
D000900:Anti-Bacterial Agents