Determination of Voriconazole Plasma Concentration by HPLC Technique and Evaluating Its Association with Clinical Outcome and Adverse Effects in Patients with Invasive Aspergillosis

Abstract

Purpose. Invasive aspergillosis is a prevalent fungal disease, especially in Asian countries with a high mortality rate. Voriconazole (VRZ) is the first choice for invasive aspergillosis treatment. Plasma concentration of this drug is unpredictable and varies among individuals. This variability is influenced by many factors leading to clinical implication. Therapeutic drug monitoring (TDM) may have a crucial role in the patients’ treatment process. The HPLC method provides sufficient specificity and sensitivity for plasma VRZ concentration determination for TDM purposes of this drug. Methods. Patients who initiated oral or intravenous VRZ for invasive aspergillosis were enrolled in this study. Demographic characteristics and clinical data, outcome, and adverse effects were documented. For each patient, the plasma sample was collected under steady-state condition and analyzed using a validated HPLC method. Results. A total of 22 measurements were performed. Fifty percent of patients were out of the therapeutic range. From them, 27.27% and 22.73% were in subtherapeutic and supratherapeutic ranges (<1 μg/mL and >5.5 μg/mL), respectively. There was a significant correlation between VRZ plasma concentration and treatment outcomes ( P = 0.022 ). Treatment failure was five times higher than treatment success in those in the subtherapeutic range. Adverse effects were observed more frequently in patients with supratherapeutic concentrations compared to those with non-supratherapeutic levels. Furthermore, the mortality rate in patients experiencing treatment failure was 2.17 times higher than those with treatment success. Conclusions. TDM of VRZ plays an important role in better evaluation of efficacy and toxicity during treatment. Therefore, determination of the drug level may be of clinical significance.

Determination of Voriconazole in Human Plasma by Liquid Chromatography Tandem Mass Spectrometry: Application in Therapeutic Drug Monitoring

“…The calibration curve ranged from 0.10 -8.00 µg/ml approximately, which was sufficient the of the voriconazole plasma trough levels in patients' samples. Comparing our method with a recently published method for voriconazole determination using standard HPLC, the running time of our method was 7.50 min compared to 20.00 min in the HPLC method [24]. The flow rate in our method was 0.30 ml/min, which relatively considered lower than most of the published methods, this has an advantage of which can be easily prepared.…”

Successful Management of Mixed Mycosis in HIV-Negative Patients With Different Immune Status: A Case Series Report

“…Additionally, lesions in 7 patients re-enlarged after the original effective treatment and were diagnosed after a second biopsy and pathological examination. Hence, based on the comprehensive patient situation, clinicians must also have rigorous procedures in the management of patients and analyze the reasons for ineffectiveness of original treatment or re-enlargement of lesions, including the sufficient triazole concentration in blood (Di Paolo et al, 2021), drug resistance (Yousefian et al, 2021), and the possibility of mixed infection with multiple pathogens such as bacteria, tuberculosis, other fungi, etc. As shown in this study, mixed mycosis is also one of the factors that needs to be considered, even in immunocompetent patients.…”

Nanotechnology-Based Approaches for Voriconazole Delivery Applied to Invasive Fungal Infections

“…The central monitoring measures have been the evaluation of CYP2C19 polymorphisms [ 190 ] and plasma drug concentration [ 189 , 191 ], in addition to the evaluation of liver function and other measures [ 192 , 193 ]. Monitoring VCZ plasma concentrations is carried out with well-standardized Liquid Chromatography coupled with Mass Spectrometry and High-Performance Liquid Chromatography methods [ 194 , 195 ].…”