Comparative effects of antifungal agents on zidovudine glucuronidation by human liver microsomes.
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).
Laboratoire de pharmacocinétique, Faculté de pharmacie, Marseille, France.
E
E
Sampol
B
B
Lacarelle
J F
JF
Rajaonarison
J
J
Catalin
A
A
Durand
D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D015725:Fluconazole / Q000494:pharmacology; D005437:Flucytosine / Q000494:pharmacology; D005965:Glucuronates / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology; D007654:Ketoconazole / Q000494:pharmacology; D008825:Miconazole / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D015215:Zidovudine / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
D000935:Antifungal Agents; D000998:Antiviral Agents; D005965:Glucuronates; D017964:Itraconazole; D015215:Zidovudine; D008825:Miconazole; D000666:Amphotericin B; D015725:Fluconazole; D005437:Flucytosine; D007654:Ketoconazole