title: Evaluation of rifaximin, placebo and lactulose in reducing the levels of benzodiazepine-like compounds in patients with liver cirrhosis: a pilot study.
abstract: Benzodiazepine-like compounds (BZDs), either taken with the diet or synthesized by intestinal bacterial flora, may represent a precipitating factor for hepatic encephalopathy (HE) in cirrhotic patients. We evaluated whether a diet and/or treatment with rifaximin or lactulose can reduce serum concentrations of BZDs in 18 cirrhotic patients without HE. Patients were given a standard diet for 7 days to keep the dietary intake of BZDs constant and were then randomized to a 7-day treatment with rifaximin 1,200 mg/day, lactulose 10-20 g three times daily, or placebo. Blood samples were collected at enrollment, at the end of the diet and drug treatment periods, and 7 days after the drug was stopped (follow-up). Serum concentrations of BZDs were measured by a radioligand binding technique after high-performance liquid chromatography extraction and purification and were expressed as diazepam equivalents (DE). No change in serum BZD concentrations was observed during the diet, while a statistically significant decrease from 105.6 +/- 66.5 to 63.5 +/- 49.5 pmol DE/ml was achieved in rifaximin-treated patients (p < 0.05) but not in patients treated with lactulose or placebo. During the followup, serum BZD concentrations returned to 104.5 +/- 74.0 pmol DE/ml in rifaximin-treated patients (p < 0.05 vs. end-treatment values), while no significant change was observed in the lactulose- and placebo-treated patients. These data indicate that control of bacterial flora with cyclic administration of rifaximin plays a pivotal role in avoiding increased plasma concentrations of BZDs, which represent a precipitating factor for HE inpatients with severe liver disease.
authors.affiliation: Internal Medicine II, Department of Internal Medicine and Medical Specialties, Università di Modena e Reggio Emilia, Modena, Italy. venturini.i@policlinico.mo.it
authors.forename: I
authors.initials: I
authors.lastname: Venturini
authors.forename: A
authors.initials: A
authors.lastname: Ferrieri
authors.forename: F
authors.initials: F
authors.lastname: Farina
authors.forename: F
authors.initials: F
authors.lastname: Cosenza
authors.forename: R
authors.initials: R
authors.lastname: Avallone
authors.forename: L
authors.initials: L
authors.lastname: Corsi
authors.forename: M
authors.initials: M
authors.lastname: Baraldi
authors.forename: M L
authors.initials: ML
authors.lastname: Zeneroli
mesh_terms: D000328:Adult; D000368:Aged; D001569:Benzodiazepines / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007792:Lactulose / Q000494:pharmacology*; D008103:Liver Cirrhosis / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010919:Placebos; D012294:Rifamycins / Q000494:pharmacology*; D000078262:Rifaximin
chemical_list: D010919:Placebos; D012294:Rifamycins; D001569:Benzodiazepines; D007792:Lactulose; D000078262:Rifaximin