ABSTRACT
BACKGROUND: Ranitidine bismuth citrate (RBC), 400 mg bid for 4 weeks, plus clarithromycin, 500 mg tid, is a regimen approved by the US Food and Drug Administration for the eradication of Helicobacter pylori in patients with duodenal ulcers. Proof that the clarithromycin portion of the regimen could be given twice daily without loss of efficacy would reduce cost and improve patient compliance. The objective of this study was to compare the H. pylori eradication rates in patients who had duodenal ulcer and were randomly assigned to 4 weeks of treatment with RBC, 400 mg bid, in conjunction with 2 weeks of therapy with either clarithromycin, 500 mg tid, or clarithromycin, 500 mg bid. PATIENTS AND METHODS: Patients who had a duodenal ulcer and were H. pylori-positive by at least two tests were randomly assigned to (1) RBC, 400 mg bid for 4 weeks, plus clarithromycin, 500 mg tid for 2 weeks, or (2) RBC, 400 mg bid for 4 weeks, plus clarithromycin, 500 mg bid for 2 weeks. H. pylori eradication was assessed 4 weeks after completion of RBC plus clarithromycin. RESULTS: Three hundred eighty-three patients from 78 centers had a duodenal ulcer and were H. pylori-positive. The modified intent-to-treat (MITT) and the per-protocol (PP) eradication rates were statistically equivalent between the twice-daily (65% MITT, 74% PP) and thrice-daily (63% MITT, 73% PP) clarithromycin treatment regimens. Incidence and types of adverse events did not differ between the two groups. CONCLUSIONS: For eradicating H. pylori in patients with duodenal ulcer, clarithromycin, 500 mg bid for 2 weeks, with RBC, 400 mg bid for 4 weeks, is equivalent to clarithromycin, 500 mg tid with RBC. The potential enhancement of patient compliance, reduced cost of clarithromycin, and equivalent efficacy would support the use of twice-daily clarithromycin in triple-therapy regimens with RBC.
Subject(s)
Bismuth/therapeutic use , Clarithromycin/therapeutic use , Helicobacter Infections/drug therapy , Helicobacter pylori/drug effects , Ranitidine/analogs & derivatives , Adult , Anti-Bacterial Agents/therapeutic use , Anti-Ulcer Agents/therapeutic use , Bismuth/adverse effects , Clarithromycin/adverse effects , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Ranitidine/adverse effects , Ranitidine/therapeutic useABSTRACT
OBJECTIVE: This study examined the effect of administration with food on the ability of ranitidine bismuth citrate to suppress and eradicate Helicobacter pylori in 41 infected volunteers. RESULTS: After a 7-day course of treatment with ranitidine bismuth citrate (400 mg b.i.d.), 90% (18/20) of subjects who received the drug with food compared with 55% (11/20) of subjects who received the drug without food tested H. pylori-negative in a 13C-urea breath test (p = 0.031). Follow-up 13C-urea breath tests performed at least 3 months after therapy showed that H. pylori was eradicated in 14% (2/14) of subjects who received ranitidine bismuth citrate with food compared with 0% (0/18) of subjects who received ranitidine bismuth citrate without food (p = 0.183). The incidence of potentially drug-related adverse events was similar regardless of whether subjects received ranitidine bismuth citrate with or without food. Headache was the most common potentially drug-related adverse event. CONCLUSIONS: These data demonstrate that administration of ranitidine bismuth citrate with food compared with without food significantly improves the suppression of H. pylori in infected volunteers.
Subject(s)
Bismuth/administration & dosage , Food , Helicobacter Infections/drug therapy , Helicobacter pylori/drug effects , Histamine H2 Antagonists/administration & dosage , Ranitidine/analogs & derivatives , Adult , Bismuth/adverse effects , Breath Tests , Carbon Radioisotopes , Double-Blind Method , Drug Administration Schedule , Drug Evaluation , Female , Follow-Up Studies , Headache/chemically induced , Headache/epidemiology , Helicobacter pylori/isolation & purification , Histamine H2 Antagonists/adverse effects , Humans , Incidence , Male , Ranitidine/administration & dosage , Ranitidine/adverse effects , Time Factors , UreaABSTRACT
A fully automated assay for the analysis of ranitidine in serum and plasma, with and without an internal standard, was validated. It utilizes robotic solid phase extraction with on-line high performance liquid chromatographic (HPLC) analysis. The ruggedness of the assay was demonstrated over a three-year period. A Zymark Py Technology II robotic system was used for serial processing from initial aspiration of samples from original collection containers, to final direct injection onto the on-line HPLC system. Automated serial processing with on-line analysis provided uniform sample history and increased productivity by freeing the chemist to analyse data and perform other tasks. The solid phase extraction efficiency was 94% throughout the assay range of 10-250 ng/mL. The coefficients of variation for within- and between-day quality control samples ranged from 1 to 6% and 1 to 5%, respectively. Mean accuracy for between-day standards and quality control results ranged from 97 to 102% of the respective theoretical concentrations.
