Document Detail

Role of therapeutic drug monitoring of voriconazole in the treatment of invasive fungal infections.
MedLine Citation:
PMID:  22478935     Owner:  NLM     Status:  In-Data-Review    
BACKGROUND: Voriconazole is a broad-spectrum, second-generation triazole antifungal agent with demonstrated efficacy in the treatment of invasive fungal infections caused by Aspergillus spp. and Candida spp. Given the characteristically poor prognosis of patients with invasive fungal infections and the protracted duration of treatment required, therapeutic monitoring of voriconazole is, in theory, an attractive method to optimize antifungal therapy.
OBJECTIVE: To determine the utility of therapeutic drug monitoring for voriconazole.
METHODS: A previously published decision-making algorithm was used to assess the currently available literature on therapeutic drug monitoring of voriconazole.
RESULTS: Several analytical methods can be used to quantify plasma or serum concentrations of voriconazole. Reasons for therapeutic monitoring of this drug include wide variability both within and between individuals secondary to drug properties, drug-drug interactions, and disease states. Furthermore, voriconazole follows nonlinear pharmacokinetics with saturable hepatic clearance. Another potential factor in favour of therapeutic drug monitoring for voriconazole is genetic polymorphism of CYP2C19, whereby patients who are homozygous for poor metabolism (about 19% of non-Indian Asians) can have 4-fold greater exposure to voriconazole. The concentrations of this drug are also greater in patients with hepatic impairment. Drug-drug interactions with other substrates of CYP2C9, CYP2C19, and CYP3A4 can also alter voriconazole concentrations. However, the correlations between plasma concentrations of voriconazole and its efficacy and toxicity are not well defined. Although lower and upper target thresholds of 0.25-2 mg/L and 4-6 mg/L, respectively, have been suggested, studies to date have not been appropriately designed or powered to reveal any definitive association.
CONCLUSIONS: Routine therapeutic drug monitoring of voriconazole is not recommended except in certain circumstances, such as lack of response to therapy or evidence of toxicity, in which case selective monitoring of voriconazole concentrations may be of clinical utility.
I Fan Kuo; Mary H H Ensom
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Canadian journal of hospital pharmacy     Volume:  62     ISSN:  0008-4123     ISO Abbreviation:  Can J Hosp Pharm     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2012-04-05     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0215645     Medline TA:  Can J Hosp Pharm     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  469-82     Citation Subset:  -    
, BSc(Pharm), PharmD, ACPR, was, at the time of writing, a student in the Faculty of Pharmaceutical Sciences, University of British Columbia. She is now a Clinical Pharmacy Specialist at St Paul's Hospital, Vancouver, British Columbia.
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