Pharmacokinetics of clarithromycin in Helicobacter pylori eradication therapy in patients with liver cirrhosis

Background: Proton pump inhibitor triple therapy with clarithromycin and me tronidazole has been widely used for Helicobacter pylori eradication. Howev er, the efficacy and the safely of this therapy in patients with liver cirr hosis have not been established. Aim: To evaluate the effect of hepatic dysfunction on metabolism of clarith romycin as it is used for H. pylori eradication therapy in patients with li ver cirrhosis, and the efficacy of eradication therapy in those patients. Methods: Serum levels of clarithromycin and its metabolite, 14-(R)-hydroxyc larithromycin, were examined in 18 subjects (five normal controls and 13 ho spitalized 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, twi ce a day) and metronidazole (250 mg, twice a day). In addition, 118 H. pylo ri-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. Howe ver, the AUC (0-6 h) values of 14-(R)hydroxyclarithromycin were significant ly lower in the Child-Pugh C group than in either the normal controls or th e 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-tr eat analysis (95% CI: 77%-85%), while in the liver cirrhosis patients it wa s 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, w ith none leading to premature withdrawal from the study. Conclusion: The 2-week low-dose lansoprazole-based triple therapy tested is a simple, effective and well-tolerated regimen for H. pylori eradication i n patients with liver cirrhosis.