Effects of lansoprazole, clarithromycin and pH gradient on uptake of [14C]amoxycillin into rat gastric tissue.
The effect of lansoprazole and clarithromycin on the uptake of [(14)C]amoxycillin into rat gastric tissue was investigated. After oral administration of [(14)C]amoxycillin, the levels of radioactivity in gastrointestinal tissue were two to 15 times higher than those in plasma. The level of radioactivity in glandular stomach was significantly higher when lansoprazole and [(14)C]amoxycillin were administered together. After intravenous administration of [(14)C]amoxycillin, there was less radioactivity in gastric tissue than after oral administration, and co-administration of lansoprazole and clarithromycin had no obvious effect. The gastric emptying rate of [(14)C]amoxycillin was not apparently affected by the co-administration of lansoprazole and clarithromycin. In vitro uptake of [(14)C]amoxycillin into gastric tissue depended on the pH, with uptake at pH 7.4 being four times greater than that at pH 4.0. The apparent synergic effects of lansoprazole are due to enhanced penetration of amoxycillin in gastric mucus and tissue by increasing intragastric pH and play an important role in the eradication of H. pylori.
Department of Drug Metabolism, Research Center, Taisho Pharmaceutical Co., Ltd, 403, Yoshino-cho 1-chome, Omiya-shi, Saitama 330-8530, Japan. S14952@ccm.taisho.co.jp
H
H
Endo
H
H
Yoshida
N
N
Ohmi
S
S
Higuchi
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000658:Amoxicillin / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D001692:Biological Transport / Q000187:drug effects; D017291:Clarithromycin / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism*; D016481:Helicobacter Infections / Q000188:drug therapy / Q000382:microbiology; D016480:Helicobacter pylori / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D064747:Lansoprazole; D008297:Male; D009853:Omeprazole / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D010406:Penicillins / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D010437:Peptic Ulcer / Q000188:drug therapy / Q000382:microbiology; D051381:Rats; D017208:Rats, Wistar
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D010406:Penicillins; D064747:Lansoprazole; D000658:Amoxicillin; D017291:Clarithromycin; D009853:Omeprazole