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)

Ketoconazole, a new broad-spectrum oral antifungal agent, has proved most useful in the treatment of superficial and systemic fungal infections. Chronic conditions like mucocutaneous candidiasis can be treated with but few side effects. An increasing number of cases have, however, been noted of severe toxic hepatitis, following ketoconazole treatment. A new case (a 61-yr-old woman treated for onychomycosis) is reported here.
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PMID:Toxic hepatitis following ketoconazole treatment. 632 Mar 58

Ketoconazole (KT) and fluconazole (FLU) are azole antifungal agents with a broad spectrum of activity against both superficial and systemic mycoses. KT is also an anticancer agent in the treatment of advanced prostate cancer. In many clinical and retrospective studies, KT has been reported to cause liver damage, i.e. chemical hepatitis. Histologic analysis of KT induced hepatotoxicity shows massive centrilobular necrosis in which the hepatotoxicity was not thought to be mediated through an immunoallergic mechanism. According to the medical literature, the pattern of hepatic injury appears to be primarily of the hepatocellular type. Because of the documented reports of KT and FLU hepatotoxicity, a cytotoxicity comparison of KT and FLU was implemented. The objective of this comparison was to evaluate the cytotoxicity of these azoles such that future mechanistic investigations of hepatotoxicity could be performed. The relative hepatotoxicity of KT and FLU was evaluated using primary cultures of postnatal rat hepatocytes. Cytotoxicity was evaluated by measuring the leakage of the cytosolic enzyme, lactate dehydrogenase (LDH), into the medium; by assessing mitochondrial reduction of 3-(4,5-dimethythiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT); by assessing lysosomal uptake of neutral red (NR); and by gross morphology (phase contrast microscopy). The cultures were exposed to various concentrations of KT (56-188 microM) for 0.5-4 h and to various concentrations of FLU (50 microM to 1.0 mM) for 0.5-6 h. There was a significant increase (P < 0.05) in LDH leakage and a large decrease in MTT reduction and lysosomal uptake of NR at 4 h for KT. One millimolar FLU had minimal effects on the LDH leakage and MTT reduction. These results demonstrate that KT is a more potent cytotoxicant than FLU; and its toxicity was expressed in a dose- and time-dependent manner.
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PMID:Comparison of ketoconazole- and fluconazole-induced hepatotoxicity in a primary culture system of rat hepatocytes. 788 87

The oral azole drugs--ketoconazole, fluconazole, and itraconazole--represent a major advance in systemic antifungal therapy. Among the three, fluconazole has the most attractive pharmacologic profile, including the capacity to produce high concentrations of active drug in cerebrospinal fluid and urine. Ketoconazole, the first oral azole to be introduced, is less well tolerated than either fluconazole or itraconazole and is associated with more clinically important toxic effects, including hepatitis and inhibition of steroid hormone synthesis. However, ketoconazole is less expensive than fluconazole and itraconazole--an especially important consideration for patients receiving long-term therapy. All three drugs are effective alternatives to amphotericin B and flucytosine as therapy for selected systemic mycoses. Ketoconazole and itraconazole are effective in patients with the chronic, indolent forms of the endemic mycoses, including blastomycosis, coccidioidomycosis, and histoplasmosis; itraconazole is also effective in patients with sporotrichosis. Fluconazole is useful in the common forms of fungal meningitis--namely, coccidioidal and cryptococcal meningitis. In addition, fluconazole is effective for selected patients with serious candida syndromes such as candidemia, and itraconazole is the most effective of the azoles for the treatment of aspergillosis.
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PMID:Oral azole drugs as systemic antifungal therapy. 819 Jan 49

To evaluate the incidence, severity, and course of ketoconazole-associated hepatic injury, 211 patients with onychomycosis were randomized by a ratio of 2:1 to receive either ketoconazole (137 patients) or griseofulvin (74 patients). All of them were seronegative for hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus (HCV) and had no biochemical abnormality before therapy. The two groups were comparable in age, sex, and pretherapy liver biochemical tests. Liver biochemical tests were followed up biweekly for 3 months, and then at monthly intervals during the remaining course of therapy. No biochemical abnormality or hepatic injury was found in patients during griseofulvin treatment. Of the patients treated with ketoconazole, 24 (17.5%; 95% confidence interval [CI], 11.1% to 23.9%) showed asymptomatic transaminase elevation. Ketoconazole was discontinued immediately after overt hepatitis developed in another 4 patients (2.9%; 95% CI, 0.1% to 5.7%) who did not succumb to hepatic decompensation. The abnormal biochemical changes in patients with overt hepatitis returned to normal after discontinuing ketoconazole. Elderly patients were more prone to develop overt hepatitis. In patients with asymptomatic liver injury, the abnormal biochemical changes gradually returned to normal despite continuing ketoconazole therapy. The results of this cohort study suggest that ketoconazole-induced overt hepatitis is more common than previously believed and that transient subclinical injury is much more common than overt hepatitis. Therapy with ketoconazole may be continued with caution in the absence of symptoms and/or hyperbilirubinemia, but should be discontinued if overt hepatitis occurs.
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PMID:Hepatic injury during ketoconazole therapy in patients with onychomycosis: a controlled cohort study. 930 18


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