Antifungals ketoconazole

POTASSIUM-SPARING DIURETICS ANTIFUNGALS -KETOCONAZOLE t eplerenone levels Inhibition of metabolism Avoid co-administration... 

MIRTAZAPINE ANTIFUNGALS- KETOCONAZOLE T mirtazapine levels Inhibition of metabolism via CYP1A2, CYP2D6 and CYP3A4 Consider alternative antifongals... 

APREPITANT ANTIFUNGALS- KETOCONAZOLE t aprepitant levels Inhibition of CYP3A4-mediated metabolism of aprepitant Use with caution clinical significance unclear monitor closely... 

ZALEPLON, ZOLPIDEM, ZOPICLONE ANTIFUNGALS -KETOCONAZOLE t zolpidem levels reported likely to occur with zaleplon and zopidone Inhibition of CYP3A4-mediated metabolism Warn patients of the risk of t sedation... 

GALANTAMINE ANTIFUNGALS -KETOCONAZOLE t galantamine levels Inhibition of 3A4-mediated metabolism of galantamine Monitor PR and BP closely, watching for bradycardia and hypotension... 

SUCRALFATE ANTIFUNGALS- KETOCONAZOLE 1 ketoconazole levels 1 absorption of ketoconazole Separate doses by at least 2-3 hours... 

Ketoconazole was the first successful, oral, broad-spectrum azole antifungal. Ketoconazole is in the imidazole... 

Clinically important, potentially hazardous interactions with azole antifungals (ketoconazole, etc.), ketoconazole, macrolide antibiotics, nefazodone, nelfinavir, ritonavir... 

They reduce absorption of tetracyclines and the antifungals, ketoconazole and itraconazole, as they are less readily soluble in an alkaline than in acid medium. 

For drugs administered oraUy, impaired gastrointestinal (GI) absorption is an important consideration. For example, aluminum ions in certain antacids or ferrous ions in oral iron supplements form insoluble chelates of tetracycline antibiotics, thereby preventing their absorption. The antifungal ketoconazole is a weak base that is only soluble at acid pH. Drugs that inhibit gastric acidity, such as the proton pump inhibitors and histamine Hj receptor antagonists, impair the dissolution and absorption of ketoconazole. 

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. 

Of the other azole antifungals, ketoconazole , (p.388) and itraconazole , (p.388), appear less likely to interact. 

The antifungal ketoconazole (Figure 6.24) has been measured in plasma using an ODS-modified silica column with methanol-aq. formic acid (0.15 mol L ) containing dibutylamine (10mmolL pH 3.0) (1 -t-1) and ED (GCE, -f l.OV vj Ag/AgCl). " Sample preparation was by LLE into hexane-ethyl acetate (1 + 1)... 

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