Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The resurgence of tuberculosis is a major problem. Increasing multiple resistance to current drugs used for therapy, non-compliance to therapy or co-morbidity are challenging problems that do not allow use of standard therapy in all patients. Quinolones are claimed to be active drugs in TB infection. Moxifloxacin shows the highest intracellular concentration in vitro and in experimental animals, but long-term tolerability is unknown. Our aim was to observe in compliant patients, not eligible for standard therapy, the effect of 6 months of therapy with moxifloxacin, isoniazid and rifampin. Nineteen patients, a control group, were observed for the same period under therapy with streptomycin, pirazinamide, rifampin, isoniazid. The patients were affected by indolent miliary pattern and concomitant lymphoma or leukemia in 3 cases; rare nodular involvement with genitourinary diseases in 3 others; segmental to lobar involvement in 4 others with concomitant multidrug resistance, bone localization, hepatitis. The control group was more uniform and showed segmental to lobar nodular involvement with pleuritis in 3 patients, together with hepatitis in 3. Monthly checks of blood gas analysis, chest X-ray, functional testing, serum titers of antibodies against antigen 60, sputum slides and complete chemical analysis were performed. A follow-up visit was performed 1 month after therapy. Patients under moxifloxacin therapy experienced no toxicity, almost complete sterilization and remission of the disease. Sterilization was obtained in 15 days. Patients under standard therapy also had a good clinical outcome, although therapy was delayed in 3 cases because of increased transaminases within the first 15 days of therapy. Moxifloxacin seems to be well tolerated and combination therapy including moxifloxacin for TB seems to be as active as the standard therapy in patients with complex illness.
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PMID:Long-term tolerance and effectiveness of moxifloxacin therapy for tuberculosis: preliminary results. 1267 17

Moxifloxacin- and rifapentine-based regimens are under investigation for the treatment of tuberculosis. However, rifapentine may induce enzymes that metabolize moxifloxacin, resulting in decreased moxifloxacin concentrations. In this phase I, two-period, sequential-design study, 13 subjects received 400 mg moxifloxacin daily for 4 days followed by daily moxifloxacin coadministered with 900 mg rifapentine thrice weekly. Pharmacokinetic analyses were performed after the 4th and 19th doses of moxifloxacin and after the 1st and 7th doses of rifapentine. For moxifloxacin, the mean area under the concentration-time curve from 0 to 24 h (AUC(0-24)) decreased by 17.2% (P = 0.0006) when the drug was coadministered with rifapentine, and the mean half-life (t(1/2)) decreased from 11.1 to 8.9 h (P = 0.0033). For rifapentine, the mean AUC(0-48) after seven thrice-weekly doses decreased by 20.3% (P = 0.0035) compared to the AUC(0-48) after the first dose, and the mean t(1/2) decreased from 18.5 to 14.8 h (P = 0.0004). The AUC(0-48) for the 25-desacetyl-rifapentine metabolite diminished 21%. Two days after completing the study drugs, one subject developed a fever and hepatitis, and another developed a flu-like illness with a rash. In conclusion, rifapentine modestly reduced moxifloxacin concentrations. Changes consistent with rifapentine autoinduction of metabolism were seen. Adverse reactions in two subjects may have represented rifamycin hypersensitivity syndrome, although some features were atypical.
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PMID:Repeated administration of high-dose intermittent rifapentine reduces rifapentine and moxifloxacin plasma concentrations. 1876 87