Decreased renal function does not alter the single-dose pharmacokinetics of metron-idazole. In patients with decreased liver function, plasma clearance of metronidazole is decreased.

Tetracycline Hydrochloride: Tetracyclines are readily absorbed and are bound to plasma proteins in varying degrees. They are concentrated by the liver in the bile and excreted in the urine and feces at high concentrations in a biologically active form.

The relative contribution of systemic versus local antimicrobial activity against H. pylori for agents used in eradication therapy has not been established.

Microbiology: Bismuth subsalicylate, metronidazole, and tetracycline administered individually as combination therapy have been shown to be active against most strains of Helicobater pylori in vitro, and in clinical infections as described in the CLINICAL STUDIES and INDICATIONS AND USAGE sections.

Helicobacter: Helicobacter pylori: In the Graham and Cutler studies, susceptibility was not performed for bismuth subsalicylate, metronidazole, or tetracycline. No adequate data were collected during the clinical studies to indicate that bismuth subsalicylate can either decrease or increase metronidazole MICs. (See CLINICAL STUDIES.)

Susceptibility testing of Helicobacter pylori isolates was performed in the P&GP study for metronidazole using agar dilution methodology1 and minimum inhibitory concentrations (MICs) were determined.

Susceptibility Testing of Helicobacter pylori: Susceptibility testing of Helicobacter pylori for metronidazole has not been standardized. No interpretivde criteria have been established for testing metron-idazole against H. pylori. The clinical significance of metronidazole MIC values against H. pylori is unknown.

CLINICAL STUDIES

Eradication of H. pylori in Patients with Active Duodenal Ulcer Disease: Investigators in the U.S. (Graham et al., 1991, 1992, and Cutler et al., 1993) and Germany (Labenz et al., 1993) studied the effect of therapy on the eradication of H. pylori using bismuth subsalicylate, metronidazole, and tetracycline hydrochlo-ride. The patient population in these studies consisted predominantly of duodenal ulcer patients with active disease. In addition to bismuth subsalicylate, metronidazole, tetra-cycline hydrochloride triple therapy, most patients were also prescribed antisecretory therapy at doses recommended for ulcer healing, with the majority receiving ranitidine. The primary efficacy variable used in these studies to determine effectiveness of therapy was H. pylori eradication, or cure of infection. Use of cure of infection as a surrogate for reduced ulcer recurrence is based on an extensive review of the literature. Eradication rates are derived from results of the randomized, controlled study of Graham et al. and the uncontrolled, nonrandomized study of Cutler et al. H. pylori eradication was defined as no positive test (culture, histology, rapid urease, or ¹³C breath test) at least 4 weeks following the end of treatment. In the analysis performed, dropouts and patients with missing H. pylori tests post-treatment were excluded. HELI-DAC Therapy (bismuth subsalicylate, metronidazole, and tetracycline hydrochloride) was effective in eradicating H. pylori.

H. pylori Eradication Rates in Patients with Active Duodenal Ulcer Disease

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