Fluconazole

Year 2018, Volume: 9 Issue: 1, 67 - 75, 25.04.2018

Selim Öncel , Sema Aşkın Keçeli

Abstract

Fluconazole is one of the most commonly-used triazoles in clinic. Like other azoles, it is a compound composed of aromatic rings. Fluconazole is effective against Candida albicans, C. dubliniensis, C. guilliermondii, C. kefyr, C. parapsilosis, C. lusitaniae, and C. tropicalis. C. krusei is naturally resistant to fluconazole and many strains of C. glabrata are either resistant or less sensitive. Fluconazole exerts its antifungal effects by inhibiting the synthesis of ergosterol, which is an integral part of the fungal cell membrane. Development of resistance is rare, but when occurs, it is in the form of cross-resistance to all azoles. In order to predict the therapeutic effectiveness of fluconazole in an individual case; the ratios of the maximum drug concentration (Cmax) on fluconazole concentration – time curve, the area under the curve, and the time needed to reach the serum drug concentration above minimum inhibitory concentration (Ttau) to the minimum inhibitory concentration should be taken into account. Fluconazole may be administered via oral or intravenous route. Oral and intravenous pharmacokinetics of fluconazole are similar since the drug is absorbed almost completely (≥%90) from the gastrointestinal system. Fluconazole penetrates into all body fluids, including cerebrospinal fluid and human milk. Main indications include blastomycosis, candidemia, systemic candida infections, candidiasis prophylaxis in high-risk patients, coccidioidomycosis, and cryptococcosis. In clinical usage, it is thought that fluconazole will interact favorably with anidulafungin, caspofungin, amphotericin B, or flucytosine in either simultaneous or sequential usage. Concomitant administration with other drugs which act as hepatic CYP2C9 or CYP3A4 isoenzyme substrates or prolong the QT interval requires close monitoring. Although fluconazole may cause a congenital anomaly syndrome in infants born to women who have received the drug in high-doses in the first trimestre, its side effects are rare.

Keywords

Fluconazole, Candida, Antifungal Agents

Flukonazol

Abstract

Flukonazol, klinikte sık kullanılan triazollerdendir. Diğer azoller gibi, aromatik halkalar içeren bir bileşiktir. Flukonazol Candida albicans, C. dubliniensis, C. guilliermondii, C. kefyr, C. parapsilosis, C. lusitaniae ve C. tropicalis'e etkilidir. C. krusei flukonazole doğal dirençli olup C. glabrata'nın birçok suşu da dirençli veya az duyarlıdır. Flukonazol, etkisini mantar hücre membranının önemli bir parçası olan fungal sterol ergosterolün sentezini engelleyerek gerçekleştirir. Flukonazole direnç gelişmesi nadir bir olaydır; ancak gerçekleştiğinde çoğunlukla tüm azollere çapraz direnç şeklindedir. Flukonazol ile tedavi başarısını öngörmede flukonazol konsantrasyonu - zaman eğrisinde maksimum ilaç konsantrasyonunun (Cmax), eğri altında kalan alanın ve minimum inhibitör konsantrasyon üzerindeki serum ilaç konsantrasyonuna ulaşmak için gerekli sürenin (Ttau) minimum inhibitör konsantrasyon değerine oranlarının değerlendirilmesi önerilmektedir. Flukonazol, oral yolla veya intravenöz infüzyon şeklinde verilir. Tamamına yakını (%≥90) mide-bağırsak yolundan emildiği için, flukonazolün oral ve intravenöz farmakokinetiği benzerdir. Flukonazol, beyin-omurilik sıvısı da dahil olmak üzere süte ve bütün vücut sıvılarına geçer. Başlıca endikasyonları blastomikozis, kandidemi ile yaygın kandida enfeksiyonları, yüksek riskli hastalarda kandidiyaz profilaksisi, koksidiyoidomikozis ve kriptokokozistir. Klinik kullanımda anidulafungin, kaspofungin, amfoterisin B ve flusitozinle birlikte kullanılmasının olumlu etkileşimlerle sonuçlanabileceği düşünülmektedir. Hepatik CYP2C9 veya CYP3A4 izoenzimlerin substratı olarak işlev gören ve QT aralığını uzatan diğer ilaçlarla birlikte kullanımı, yakın izlem gerektirir. Gebeliklerinin ilk trimesterinde yüksek dozda flukonazol alan kadınların bebeklerinde konjenital bir anomali sendromuna neden olabilse de yan etkileri nadirdir.

Keywords

flukonazol, kandida, Antifungal ajanlar

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