Abstract:
:Fluconazole, a triazole, inhibits synthesis of ergosterol. The key enzyme of antifungal activity is C-14-Demethylase, which itself depends on Cytochrom-P-450. So drugs that inhibit or induce this enzyme lead to interactions that have to be considered when dosing fluconazole. Oral bioavailability is more than 90% after a 50 mg dose, peak levels are reached after 0.5-1.5 h (empty stomach) or 4 h (with nutrition). A loading dose on the first day leads to steady state levels on the second day. Because of the hydrophilic properties fluconazole penetrates very well into body fluids and tissues. With the M27 method conditions regarding susceptibility testing have been standardized and minimal inhibitory concentrations (MICs) have been established for fluconazole. The linear relation between dose and concentration offers the possibility to treat less susceptible fungi with higher doses, but only when MICs correlate with efficacy and higher doses are tolerated as well. Prospectively randomized studies are rare. With the limited data indications as consensus recommendations are demonstrated. Data regarding high dose therapy with fluconazole in surgical or intensive care patients demonstrate efficacy and tolerability. In addition dosage has to be adjusted in case of haemofiltration or haemodialysis. At last future options for high dose fluconazole are discussed.
journal_name
Mycosesjournal_title
Mycosesauthors
Silling Gdoi
10.1111/j.1439-0507.2002.tb04768.xsubject
Has Abstractpub_date
2002-01-01 00:00:00pages
39-41eissn
0933-7407issn
1439-0507journal_volume
45 Suppl 3pub_type
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