Vol.67 No.5 September 2019
Benefits of measuring plasma voriconazole concentrations in hospitals
1)Department of Pharmacy, Toho University Omori Medical Center, 6-11-1 Omori-nishi, Ota-ku, Tokyo, Japan
2)Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Toho University
3)Department of Pharmacy, National Defense Medical College Hospital
Abstract
Plasma concentrations of voriconazole (VRCZ), which is a triazole antifungal agent, show larger interindividual variability than those of other azole antifungal agents. This is because of the nonlinear pharmacokinetics of VRCZ due to its saturated metabolism and the genetic polymorphism of CYP2C19. Because VRCZ can induce adverse reactions, such as hepatotoxicity and visual disturbances, therapeutic drug monitoring (TDM) is necessary to optimize treatment with this drug.
Until date, several techniques have been developed for measuring the plasma VRCZ concentrations, including microbiological assays, high-performance liquid chromatography (HPLC) combined with ultraviolet, and liquid chromatography-mass spectrometry (LC-MS). Although most of these methods are useful, we adopted an HPLC-based method, which has been demonstrated to show adequate precision and accuracy, with a simple sample preparation process and short run time of 15 min. We proposed that this assay could be employed to determine the appropriate dosage regimen for VRCZ therapy, to ensure its efficacy and safety.
Indeed, we have started measuring plasma VRCZ concentrations at our hospital since 2009. In recent years, the number of requests for measurement of plasma VRCZ concentrations from clinicians has been increasing, because TDM has been proven to be important for optimizing VRCZ therapy. This monitoring is important because it is difficult to estimate the plasma VRCZ concentrations in individual patients and to control the myriad clinical factors that affect the drug's clinical efficacy and safety. Therefore, we recommend the establishment of a simple, rapid, and clinically applicable measurement system for measuring the plasma VRCZ concentrations in hospitals. Such a system could further improve the clinical outcomes of treatment for fungal infections, suppress the emergence of antimicrobial resistance, and reduce the treatment costs. In addition, we consider it necessary to improve the human resources and laboratory capacity in hospitals to facilitate measurement of the plasma VRCZ concentrations.
In this review, we summarize the features of VRCZ and method of measurement of the plasma concentration of VRCZ, and discuss the benefits of plasma VRCZ concentration measurement in hospitals.
Key word
voriconazole, therapeutic drug monitoring, high-performance liquid chromatography, antifungal stewardship
Received
September 20, 2018
Accepted
March 7, 2019
Jpn. J. Chemother. 67 (5): 556-566, 2019
