Abstract
Zidovudine (ZDV) is extensively metabolised by the liver to an inactive glucuronide (GZDV). Since ZDV is often administered with antimycotic drugs, we studied the effect of six systemic antifungal agents on the in vitro glucuronidation of ZDV by human liver microsomes. 5-fluorocytosine and itraconazole had no inhibitory effect whereas amphotericine B, ketoconazole, miconazole and fluconazole inhibited in vitro GZDV formation (Ki values were 0.13, 0.08, 0.18 and 1.4 mM respectively).
MeSH terms
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Amphotericin B / pharmacology
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Antifungal Agents / pharmacology*
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Antiviral Agents / chemistry
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Antiviral Agents / metabolism*
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Antiviral Agents / pharmacology
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Chromatography, High Pressure Liquid
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Fluconazole / pharmacology
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Flucytosine / pharmacology
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Glucuronates / chemistry
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Glucuronates / metabolism
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Humans
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Itraconazole / pharmacology
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Ketoconazole / pharmacology
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Miconazole / pharmacology
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Microsomes, Liver / drug effects
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Microsomes, Liver / metabolism*
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Zidovudine / chemistry
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Zidovudine / metabolism*
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Zidovudine / pharmacology
Substances
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Antifungal Agents
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Antiviral Agents
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Glucuronates
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Itraconazole
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Zidovudine
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Miconazole
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Amphotericin B
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Fluconazole
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Flucytosine
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Ketoconazole