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

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 i...

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Main Authors: Sahar Yousefian, Farzaneh Dastan, Majid Marjani, Payam Tabarsi, Saghar Barati, Nahid Shahsavari, Farzad Kobarfard
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Canadian Journal of Infectious Diseases and Medical Microbiology
Online Access:http://dx.doi.org/10.1155/2021/5497427
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author Sahar Yousefian
Farzaneh Dastan
Majid Marjani
Payam Tabarsi
Saghar Barati
Nahid Shahsavari
Farzad Kobarfard
author_facet Sahar Yousefian
Farzaneh Dastan
Majid Marjani
Payam Tabarsi
Saghar Barati
Nahid Shahsavari
Farzad Kobarfard
author_sort Sahar Yousefian
collection DOAJ
description 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.
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spelling doaj-art-97b24b5c61434b79b993b8d6aab8fd442025-08-20T02:10:07ZengWileyCanadian Journal of Infectious Diseases and Medical Microbiology1712-95321918-14932021-01-01202110.1155/2021/54974275497427Determination of Voriconazole Plasma Concentration by HPLC Technique and Evaluating Its Association with Clinical Outcome and Adverse Effects in Patients with Invasive AspergillosisSahar Yousefian0Farzaneh Dastan1Majid Marjani2Payam Tabarsi3Saghar Barati4Nahid Shahsavari5Farzad Kobarfard6Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, IranClinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NIRTLD), Shahid Beheshti University of Medical Sciences, Tehran, IranClinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NIRTLD), Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, IranPurpose. 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.http://dx.doi.org/10.1155/2021/5497427
spellingShingle Sahar Yousefian
Farzaneh Dastan
Majid Marjani
Payam Tabarsi
Saghar Barati
Nahid Shahsavari
Farzad Kobarfard
Determination of Voriconazole Plasma Concentration by HPLC Technique and Evaluating Its Association with Clinical Outcome and Adverse Effects in Patients with Invasive Aspergillosis
Canadian Journal of Infectious Diseases and Medical Microbiology
title Determination of Voriconazole Plasma Concentration by HPLC Technique and Evaluating Its Association with Clinical Outcome and Adverse Effects in Patients with Invasive Aspergillosis
title_full Determination of Voriconazole Plasma Concentration by HPLC Technique and Evaluating Its Association with Clinical Outcome and Adverse Effects in Patients with Invasive Aspergillosis
title_fullStr Determination of Voriconazole Plasma Concentration by HPLC Technique and Evaluating Its Association with Clinical Outcome and Adverse Effects in Patients with Invasive Aspergillosis
title_full_unstemmed Determination of Voriconazole Plasma Concentration by HPLC Technique and Evaluating Its Association with Clinical Outcome and Adverse Effects in Patients with Invasive Aspergillosis
title_short Determination of Voriconazole Plasma Concentration by HPLC Technique and Evaluating Its Association with Clinical Outcome and Adverse Effects in Patients with Invasive Aspergillosis
title_sort determination of voriconazole plasma concentration by hplc technique and evaluating its association with clinical outcome and adverse effects in patients with invasive aspergillosis
url http://dx.doi.org/10.1155/2021/5497427
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