Azole antifungal drugs other effects

The azole antifungal drugs, as already noted, exert their pharmacodynamic effects through the inhibition of the synthesis of fungal steroids. However, they have also been found to have similar effects on mammalian steroidogenesis. " Studies in vitro showed that ketoconazole and other azoles decreased the... 

Nelfinavir mesylate is a peptidomimetic drug that is effective in HIV-1 and HIV-2 wild-type and ZDV-resistant strains, with median effective dose concentrations ranging from 9 to 60 nM (95% effective dose, 0.04 mg/mL) (98). After IV administration, the elimination half-life of nelfinavir was approximately 1 hour. In combination with D4T, nelfinavir reduced HIV viral load by approximately 98% after 4 weeks. It is well tolerated when used with azole antifungals (ketoconazole, fluconazole, or itraconazole) or macrolide antibiotics (erythromycin, clarithromycin, or azithromycin) however, it causes diarrhea and other side effects common to nonnucleoside drugs. Following oral administration, nelfinavir peak levels in plasma ranged from 0.34 mg/mL (10 mg/kg in the dog) to 1.7 mg/mL (50 mg/kg in the rat). In the dog, nelfinavir was slowly absorbed, and bioavailability was 47%. The drug appeared to be metabolized in the liver, and the major excretory route was in feces. 

Zaleplon, zolpidem and zopiclone are metabolised by several cytochrome CYP450 isoenzymes and it has been suggested that because of this, other drugs which affect a particular isoenzyme such as CYP3A4, may have less effect on their metabolism. However, their pharmacokinetics are affected by potent inducers such as rifampicin and by inhibitors such as the azole antifungals. Buspirone undergoes CYP3A4-mediated metabolism in the liver. 

Itraconazole [it ra KON a zole] is a recent addition to the azole family of antifungal agents. Like fluconazole it is a synthetic triazole, and it also lacks the endocrinologic side effects of ketoconazole. Its mode of action is the same as that of the other azoles. Itraconazole is now the drug of choice for the treatment of blastomycosis. Unlike ketoconazole, it is effective in AIDS-associated histoplasmosis. However, current studies show that it may also be effective in the treatment of aspergillosis, candidemia, coccidioidomycosis, and cryptococcosis. Thus it has a broad antifungal spectrum. 

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