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Why is Therapeutic Drug Monitoring for Voriconazole Essential in the Treatment of Fungal Infections

Parisa Badiee and Zahra Hashemizadeh*

Prof. Alborzi Clinical Microbiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

*Corresponding Author:
Hashemizadeh Zahra
Department of Clinical Microbiology
Prof. Alborz Research Centre, Namazee Hospital Zand Ave., Shiraz, Iran
Tel: 9871-3647-4292
Fax: 98 71-3647-4303
E-mail: [email protected]

Received Date: May 18, 2016; Accepted Date: June 16, 2016; Published Date: June 26, 2016

Citation: Badiee P, Hashemizadeh Z (2016) Why is Therapeutic Drug Monitoring for Voriconazole Essential in the Treatment of Fungal Infections. Clin Microbiol 5:250. doi: 10.4172/2327-5073.1000250

Copyright: © 2016 Badiee P, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Fungal infections are frequent life-threatening complications in immune compromised patient sand in patients admitted in ICU wards [1]. Voriconazole (VRC) is a second-generation wide-spectrum antifungal triazole recommended for the treatment of potentially lifethreatening fungal infections including invasive aspergillosis, disseminated candidasies, and other infections caused by Fusarium and Scedosporium spp. [2,3]. This compound can be administered as an intravenous infusion and oral formulations. Studies with healthy volunteers demonstrated bioavailability of >90% after oral administration [4]. A steady-state level is achieved in three days with two loading doses of 400 mg for the first day, followed by a maintenance dose of 200 mg every 12 hours thereafter [5]. Investigations have shown both within and between individual's variability in VRC steady-state plasma concentration and non-linear pharmacokinetics due to saturation of its metabolism with respect to dose. This variability was observed with both intravenous and oral formulations [6]. Other pharmacokinetic variability's include decreased absorption of oral VRC with meals, interactions with comedications, patient's age, hepatic inefficiency and genetic polymorphisms of cytochrome P450 (CYP) iso-enzymes, mainly CYP2C19 enzyme [6,7]. Generally accepted plasma level for VRC is 1-5.5 mg/L. There have been reports that a clear relationship exists between drug concentration and drug response. High levels (>5.5 mg/L) are associated with variant adverse drug reactions. The most frequently side effects of VRC are vomiting , nausea , fever, skin rash, vision color changes, visual disturbances, blurred vision, hepatotoxicity, liver enzyme elevation, encephalopathy, and electrolyte abnormalities. Levels of VRC (<1 mg/L) have been associated with therapeutic failures and breakthrough infection [8]. In addition, using recommended dosing regimens in both adults and pediatrics has shown a significant relationship between VRC plasma levels and clinical efficacy and/or toxicity indicating a need for therapeutic drug monitoring (TDM). TDM may enable clinicians to make a better use of VRC, and is recommended as a tool to individualize VRC doses and may be particularly helpful in the context of preventing drug-related side effects. Therefore, TDM of VRC concentrations is highly recommended to maximize efficacy and minimize adverse events [9].

To perform therapeutic drug monitoring, several available analytic methods enabled quantified the VRC concentration in human plasma or serum. Most of these assays use high-performance liquid chromatography methods with ultra-violet detection (HPLC-UV) or coupled with mass spectrophotometry. Other methods such as bioassays or microbiological assays have also been investigated as a valid alternative to chromatographic methods. Bioassays can determine the total antifungal activity of a drug, conversely, HPLC or ultra-HPLC quantify the concentrations of VRC but cannot assess its activity [10].

In conclusion, Candida and Aspergillus spp. are the most common causes of invasive fungal infections with high morbidity and mortality in immune compromised patients [1,11,12]. Voriconazole, compared with other antifungal agents, has potent activity against a broader spectrum of clinically significant fungal pathogens, including Aspergillus, Candida spp., especially Candida krusei and Candida glabrata which resist other antifungal agents [13]. Using VRC in combination with TDM can serve as the best method for the survival of patients.


The authors would like to thank Dr. Hassan Khajea PhD, for copy editing of the manuscript.


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