title: Pharmacokinetics of clarithromycin in Helicobacter pylori eradication therapy in patients with liver cirrhosis.
abstract: BACKGROUND
  Proton pump inhibitor triple therapy with clarithromycin and metronidazole has been widely used for Helicobacter pylori eradication. However, the efficacy and the safety of this therapy in patients with liver cirrhosis have not been established.
  
  
  OBJECTIVE
  To evaluate the effect of hepatic dysfunction on metabolism of clarithromycin as it is used for H. pylori eradication therapy in patients with liver cirrhosis, and the efficacy of eradication therapy in those patients.
  
  
  METHODS
  Serum levels of clarithromycin and its metabolite. 14-(R)-hydroxyclarithromycin, were examined in 18 subjects (five normal controls and 13 hospitalized patients with liver cirrhosis) on a selected day between days 7 and 10 of a 2-week course of eradication therapy. This therapy consisted of lansoprazole (30 mg, once a day) together with clarithromycin (200 mg, twice a day) and metronidazole (250 mg, twice a day). In addition, 118 H. pylori-positive out-patients, 88 with peptic ulcer and 30 with liver cirrhosis, underwent the same eradication therapy.
  
  
  RESULTS
  Values for the area under the 0-6 h concentration-time curve (AUC) for clarithromycin were not significantly different among the groups. However, the AUC (0-6 h) values of 14-(R)-hydroxyclarithromycin were significantly lower in the Child-Pugh C group than in either the normal controls or the Child-Pugh A/B group. The cure rate for the peptic ulcer patients was 84% on a per protocol analysis (95% CI: 80%-88%) and 81% on an intention-to-treat analysis (95% CI: 77%-85%), while in the liver cirrhosis patients it was 89% in a per protocol analysis (95% CI: 78%-99%) and 83% in an intention-to-treat analysis (95% CI: 70%-97%). Mild adverse effects were observed in 10% of the peptic ulcer patients and 13% of the liver cirrhosis patients, with none leading to premature withdrawal from the study.
  
  
  CONCLUSIONS
  The 2-week low-dose lansoprazole-based triple therapy tested is a simple, effective and well-tolerated regimen for H. pylori eradication in patients with liver cirrhosis.
authors.affiliation: Second Department of Internal Medicine, Faculty of Medicine, Fukui Medical University, Japan. azuma@fmsrsa.fukui-med.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Azuma
authors.forename: S
authors.initials: S
authors.lastname: Ito
authors.forename: H
authors.initials: H
authors.lastname: Suto
authors.forename: Y
authors.initials: Y
authors.lastname: Ito
authors.forename: H
authors.initials: H
authors.lastname: Miyaji
authors.forename: Y
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: T
authors.initials: T
authors.lastname: Kato
authors.forename: M
authors.initials: M
authors.lastname: Kuriyama
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000897:Anti-Ulcer Agents / Q000008:administration & dosage; D017291:Clarithromycin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000378:metabolism*; D016480:Helicobacter pylori; D006801:Humans; D064747:Lansoprazole; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage; D008875:Middle Aged; D009853:Omeprazole / Q000008:administration & dosage / Q000031:analogs & derivatives; D010437:Peptic Ulcer / Q000188:drug therapy / Q000382:microbiology
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D064747:Lansoprazole; D008795:Metronidazole; D017291:Clarithromycin; D009853:Omeprazole