Systemic Antifungal Agents

Fluconazole (4) (s the first member of a new generation of orally acti ve antifungal agents, highly effective in the treatment of dermal and vaginal infections [6, 7] S-Fluorocyrtosine (5) is also used to treat serious systemic fungal infections [5]... 

Stopher and Gage used size-exclusion chromatography (SEL) coupled to reversed phase HPLC for the direct injection of plasma in the analysis of an antifungal agent, voriconazole (12). Their system consisted of three columns, i.e. first a size-exclusion... 

Systemic adverse effects associated with vaginal azoles are less frequent than with oral products. Local discomfort such as burning may occur with the first application. Fifteen percent of patients experience gastrointestinal side effects with orally administered antifungal agents.13 Oral ketoconazole is associated with hepatic toxicity at a rate of 1 in 15,000.14... 

P450 system Drugs that may be affected by proton pump inhibitors include benzodiazepines, clarithromycin, cyclosporine, disulfiram, digoxin, azole antifungal agents, hydantoins, cilostazol, salicylates, sulfonylureas, and warfarin. 

Mechanism of Action An antifungal agent that inhibits ergosterol synthesis. Therapeutic Effect Destroys cytoplasmic membrane integrity of fungi. Fungicidal. Pharmacokinetics Low systemic absorption. Absorbed and distributed in each layer... 

Antifungal agents are used in the treatment of topical and systemic fungal infection. They can be classified as systemic or topical antifungal agents and some are used both systemically as well as topically in the form of powder, ointment and vaginal tablets etc. They are classified as in table 9.7.1. 

Inhibitors of the CYP3A4 isoenzyme could increase systemic dofetilide exposure. Inhibitors of this isoenzyme (e.g., macrolide antibiotics, azole antifungal agents, protease inhibitors, serotonin reuptake inhibitors, amiodarone, cannabinoids, diltiazem, grapefruit juice, nefazadone, norfloxacin, quinine, and zafirlukast) should be cautiously coadministered with TIKOSYN, because they can potentially increase dofetilide levels... 

Cyclosporin is metabolised by the hepatic cytochrome P-450 enzyme system, and enzyme induction by phenobarbital, phenytoin, carbamazepine, or rifampicin will drastically increase the clearance of cyclosporin. Concurrent administration of these drugs has caused rejection of transplanted organs. Conversely, the use of enzyme inhibitors, such as erythromycin or the azole antifungal agents, e.g. ketoconazole, will increase the blood concentrations of cyclosporin leading to an increased risk of toxic side effects. 

While Via antagonists have been synthesized, none of these have been reported to penetrate the central nervous system efficiently. In 2007, the same authors have identified the azetidinone LY307174 (I, Fig. 39), for a screening based on 59% molecular similarity to ketoconazole (II, Fig. 39), a marketed antifungal agent... 

Lyman, C. A. and Walsh, T. J. (1992). Systemically administered antifungal agents. A review of their clinical pharmacology and therapeutic applicaticBsugs, 44, 9-35. 

Medoff, G., Brajtburg, J., Kobayashi, G. S., and Bolard, J. (1983). Antifungal agents useful in therapy of systemic fungal infectionsftnn. Rev. Pharmacol. Toxicol., 23, 303. 

Agents used to treat common fungal infections are listed in Tables 35-1 and 35-2. As indicated in Table 35-1, certain drugs can be administered systemic ally to treat infections in various tissues. Other agents are more toxic their use is limited to local or topical application for fungal infections in the skin and mucous membranes (Table 35-2). The use of systemic and topical antifungal agents is addressed in more detail below. 

The antifungal agents that can be administered sys-temically by oral or intravenous routes are listed here. These agents are often used to treat invasive (deep) fungal infections in the body, or they can be administered systemically to treat more superficial infections that have disseminated over a large area of the skin or subcutaneous tissues. The clinical use, mechanism of action, and potential adverse effects of these drugs are addressed here. 

USE OF SYSTEMIC ANTIFUNGAL AGENTS IN INVASIVE AND DISSEMINATED MYCOSES ... 

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