Antifungal azoles

Lewis, D. F. V., Wiseman, A., and Tarbit, M. H. (1999) Molecular modeling of lanosterol 14-alpha-demethylase (CYP51) from Saccharomyces cerevisiae via homology with CYP102, a unique bacterial cytochrome P450 isoform quantitative structure-activity relationships (QSARs) within two related series of antifungal azole derivatives../. Enz. Inhib. 14, 175-192. 

Trosken, E.R., Adamska, M., Arand, M., Zarn, J.A., Patten, G., Volkel, W. and Lutz, W.K. (2006) Comparison of lanosterol-14 alpha-demethylase (CYP51) of human and Candida albicans for inhibition by different antifungal azoles. Toxicology, 228, 24-32. 

The risk of myopathy appears to be increased by high levels of HMG-CoA reductase inhibitory activity in plasma. Lovastatin is metabolized by the CYP isoform 3A4. Certain drugs, that share this metabolic pathway can raise the plasma levels of lovastatin and may increase the risk of myopathy. These include cyclosporine, itraconazole, ketoconazole and other antifungal azoles, the macrolide antibiotics erythromycin and clarithromycin, HIV protease inhibitors, the antidepressant nefazodone, or large quantities of grapefruit juice (greater than 1 quart daily)... 

The antifungal azoles inhibit CYP isozymes and can therefore interact with some statins. 

Mechanism of Action. Like the systemic azoles, clotrimazole and other topical antifungal azoles work by inhibiting the synthesis of key components of the fungal cell membrane that is, these drugs impair production of membrane sterols, triglycerides, and phospholipids.9 Loss of these components results in the membrane s inability to maintain intracellular homeostasis, leading to death of the fungus. 

Azole antifungals -azole Fluconazole, miconazole Fungal infections [35]... 

Upadhayaya, R. S., Sinha, N., Jain, S., Kishore, N., Chandra, R., Arora, S.K. Optically active antifungal azoles synthesis and antifungal activity of (2R,3S)-2-(2,4-difluorophenyl)-3-(5-[2-[4-arylpipera-zin-l-yl]ethyl]tetrazol-2-yl/l-yl)-l-[ 1,2,4]-triazol-l-yl-butan-2-ol. Bioorg. Med. Chem. 2004, 12, 2225-2238. 

In an in vitro study of midazolam biotransformation using human liver microsomes, midazolam metabolism was competitively inhibited by the antifungal azoles keto-conazole, itraconazole, and fluconazole, and the antidepressant fluoxetine and its metabolite norfluoxetine (55). The degree of inhibition was consistent with the inhibition reported in pharmacokinetic studies, and suggests that in vitro assay is useful for predicting significant interactions. 

VASODILATOR ANTI HYPERTENSIVES ANTIFUNGALS-AZOLES t bosentan levels Azoles inhibit CYP3A4 and CYP2C9 Monitor LFTs closely... 

ANTIMIGRAINE DRUGS-5-HT1 AGONISTS ANTIFUNGALS-AZOLES t levels of almotriptan and eletriptan Inhibited metabolism Avoid co-administration... 

TOREMIFENE ANTIFUNGALS-AZOLES t plasma concentrations of toremifene Due to inhibition of metabolism of toremifene by the CYP3A4 isoenzymes by ketoconazole Clinical relevance is uncertain. Necessary to monitor for clinical toxicities... 

SIROLIMUS ANTIFUNGALS - AZOLES t sirolimus levels Inhibition of metabolism of sirolimus Avoid co-administration... 

ANTACIDS ANTIFUNGALS-AZOLES 1 plasma concentration of itraconazole and ketoconazole, with risk of therapeutic failure Itraconazole absorption in capsule form requires an acidic gastric environment, and thus absorption would be 1 Separate administration of agents that 1 gastric acidity by 1-2 hours. However, absorption of itraconazole liquid solution does not require an acidic environment it could be used instead and does not need to be given with food. Fluconazole absorption is not pH-dependent, so this is a suitable alternative... 

PHOSPHODIESTERASE TYPE 5 INHIBITORS ANTIFUNGALS-AZOLES T sildenafil, tadalafil and vardenafil levels Inhibition of metabolism l dose of these phosphodiesterase type 5 inhibitors... 

Other inhibitors of HZ formation are thought to act similarly to the quinohne family. Binding of the antifungal azole-based drugs (clotrimazole, ketoconazole, and miconazole) to heme is thought to damage parasite cell membranes and cause... 

The antibacterial, antiprotozoal and anthelminthic members of this group are described in the appropriate sections. Antifungal azoles comprise the following ... 

In evaluating possible antagonism between amphotericin and antifungal azoles, details of the experimental set-up are crucial. When filamentous fungi were exposed to subfungicidal concentrations of azoles, before exposure to an amphotericin -I- azole combination, antagonism could always be shown both in vitro and in vivo (148-150). 

Drug interactions with the antifungal azoles are common for several reasons ... 

For details of interactions with individual antifungal azoles, see individual monographs (fluconazole, itraconazole, ketoconazole, miconazole, and voriconazole). 

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