1,721,112 research outputs found
Rifaximin in the management of colonic diverticular disease.
No full textRifaximin is a rifamycin derivative that acts by inhibiting bacterial RNA
synthesis. Since it is virtually unabsorbed after oral administration, its
bioavailability within the GI tract is high, with intraluminal and fecal drug
concentrations largely exceeding the minimum inhibitory concentration values
observed in vitro against a broad spectrum of bacteria, including Gram-positive
and Gram-negative bacteria, both aerobes and anaerobes. The GI tract, therefore,
represents the primary therapeutic target and the disorders in which intestinal
bacteria have a pathogenic role represent the main indication. This is the case
with colonic diverticular disease. As a consequence, the broad antibacterial
activity of rifaximin appears to be of value in the treatment of this clinical
condition. Clinical trials have provided evidence of the substantial benefit of
rifaximin in diverticular disease. Indeed, available data show the efficacy of
the drug in achieving symptomatic relief in patients with uncomplicated disease.
A therapeutic gain of approximately 30%, compared with fiber supplementation
only, can be expected after cyclic administration of rifaximin for 12 months.
However, its value in the prevention of inflammatory complications of the disease
needs to be further explored. Recent studies have shown some evidence of synergy
between rifaximin and mesalazine and suggest that a combined treatment could be
worthwhile in selected subsets of patients with diverticular disease
Letter: can the overall gastrointestinal safety of celecoxib be extended to all COX-2-selective agents?
No full textNo abstract available
Impact of crystal polymorphism on the systemic bioavailability of rifaximin, an antibiotic acting locally in the gastrointestinal tract, in healthy volunteers.
Full text linkBACKGROUND: Rifaximin is an antibiotic, acting locally in the gastrointestinal
tract, which may exist in different crystal as well as amorphous forms. The current marketed rifaximin formulation contains polymorph alpha, the systemic bioavailability of which is very limited. This study compared the pharmacokinetics of this formulation with those of the amorphous form.
METHODS: Amorphous rifaximin was specifically prepared for the study and formulated as the marketed product. Two doses (200 mg and 400 mg) of both formulations were given to two groups of 12 healthy volunteers of either sex according to a single-blind, randomized, two-treatment, single-dose, two-period, cross-over design. Plasma and urine samples were collected at preset times (for 24 hours or 48 hours, respectively) after dosing, and assayed for rifaximin concentrations by high-performance liquid chromatography-mass spectrometry.
RESULTS: For both dose levels, peak plasma concentration, area under the concentration-time curve, and cumulative urinary excretion were significantly higher after administration of amorphous rifaximin than rifaximin-α. Ninety percent confidence intervals for peak plasma concentration, area under the concentration-time curve, and urinary excretion ratios were largely outside the upper limit of the accepted (0.80-1.25) range, indicating higher systemic bioavailability of the amorphous rifaximin. The few adverse events recorded were not serious and not related to the study medications.
CONCLUSION: Rifaximin-α, a crystal polymorph, does differ from the amorphous form, the latter being systemically more bioavailable. In this regard, care must be taken when using - as a medicinal product - a formulation containing even small amounts of amorphous form, which may alter the peculiar pharmacologic properties of this poorly absorbed antibiotic
Proton pump inhibitors in GORD . An overview of their pharmacology, efficacy and safety.
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Use of Pharmacogenetics to Optimize Immunosuppressant Therapy in Kidney-Transplanted Patients
No full textImmunosuppressant drugs (ISDs) are routinely used in clinical practice to maintain organ transplant survival. However, these drugs are characterized by a restricted therapeutic index, a high inter- and intra-individual pharmacokinetic variability, and a series of severe adverse effects. In particular, genetic factors have been estimated to play a role in this variability because of polymorphisms regarding genes encoding for enzymes and transporters involved in the ISDs pharmacokinetic. Several studies showed important correlations between genetic polymorphisms and ISDs blood levels in transplanted patients; therefore, this review aims to summarize the pharmacogenetics of approved ISDs. We used PubMed database to search papers on pharmacogenetics of ISDs in adults or pediatric patients of any gender and ethnicity receiving immunosuppressive therapy after kidney transplantation. We utilized as search term: “cyclosporine or tacrolimus or mycophenolic acid or sirolimus or everolimus and polymorphism and transplant”. Our data showed that polymorphisms in CYP3A5, CYP3A4, ABCB1, and UGT1A9 genes could modify the pharmacokinetics of immunosuppressants, suggesting that patient genotyping could be a helpful strategy to select the ideal ISDs dose for each patient
Clinical pharmacology and safety profile of esomeprazole, the first enantiomerically pure proton pump inhibitor.
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