Deciphering the Relationship Between the Trough Concentration of Posaconazole and Its Efficacy and Safety in Chinese Patients With Hematological Disorders
Posaconazole (PCZ) is effective in preventing and salvage treatment invasive fungal infections in patients with hematologic disorders. However, PCZ displays highly variable individual pharmacokinetics affecting its efficacy and safety. To investigate the correlation between PCZ concentration and eff...
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doaj-126ef41a89654c89b0e4000e2bbb1ac62020-11-25T03:44:57ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-10-011110.3389/fphar.2020.575463575463Deciphering the Relationship Between the Trough Concentration of Posaconazole and Its Efficacy and Safety in Chinese Patients With Hematological DisordersMeng-Meng Jia0Meng-Meng Jia1Qi-Wen Zhang2Qi-Wen Zhang3Zi-Fei Qin4Zi-Fei Qin5Run-Qing Lu6Xue-Ke Tian7Xue-Ke Tian8Jing Yang9Jing Yang10Xiao-Jian Zhang11Xiao-Jian Zhang12Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, ChinaDepartment of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, ChinaPosaconazole (PCZ) is effective in preventing and salvage treatment invasive fungal infections in patients with hematologic disorders. However, PCZ displays highly variable individual pharmacokinetics affecting its efficacy and safety. To investigate the correlation between PCZ concentration and efficacy and safety, the following key influencing factors were explored. A total of 285 trough plasma concentrations (Cmin) of 81 Chinese patients receiving PCZ oral suspension for prophylaxis or treatment of invasive fungal infections were collected in this study. The relationships between Cmin values and clinical response and hepatotoxicity were investigated as well as the incidence of clinical response under different Cmin values of PCZ with a logistic regression model. The concentration of PCZ showed remarkable differences among patients with haematologic disorders. PCZ Cmin values of 0.76 and 1.0 µg/mL were both associated with an over 80% probability of successful response to prophylaxis and treatment of fungal infections, respectively. No association between Cmin values and hepatotoxicity was noted (P > 0.05). Gender, albumin, and co-administration of proton pump inhibitor (PPI) were identified as independent factors influencing PCZ Cmin by multiple linear regression analysis. Furthermore, patients’ C-reactive protein (CRP), albumin, and co-administration of PPI exhibited significant effects on the therapeutic window of patients receiving PCZ for prophylaxis. The plasma concentration is closely associated with therapeutic efficacy of PCZ. It is necessary to adjust the dosing regimens based on PCZ Cmin to obtain an optimal therapeutic response.https://www.frontiersin.org/article/10.3389/fphar.2020.575463/fullposaconazoleinvasive fungal infectionpharmacokineticsdrug monitoringhematological disorders |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Meng-Meng Jia Meng-Meng Jia Qi-Wen Zhang Qi-Wen Zhang Zi-Fei Qin Zi-Fei Qin Run-Qing Lu Xue-Ke Tian Xue-Ke Tian Jing Yang Jing Yang Xiao-Jian Zhang Xiao-Jian Zhang |
spellingShingle |
Meng-Meng Jia Meng-Meng Jia Qi-Wen Zhang Qi-Wen Zhang Zi-Fei Qin Zi-Fei Qin Run-Qing Lu Xue-Ke Tian Xue-Ke Tian Jing Yang Jing Yang Xiao-Jian Zhang Xiao-Jian Zhang Deciphering the Relationship Between the Trough Concentration of Posaconazole and Its Efficacy and Safety in Chinese Patients With Hematological Disorders Frontiers in Pharmacology posaconazole invasive fungal infection pharmacokinetics drug monitoring hematological disorders |
author_facet |
Meng-Meng Jia Meng-Meng Jia Qi-Wen Zhang Qi-Wen Zhang Zi-Fei Qin Zi-Fei Qin Run-Qing Lu Xue-Ke Tian Xue-Ke Tian Jing Yang Jing Yang Xiao-Jian Zhang Xiao-Jian Zhang |
author_sort |
Meng-Meng Jia |
title |
Deciphering the Relationship Between the Trough Concentration of Posaconazole and Its Efficacy and Safety in Chinese Patients With Hematological Disorders |
title_short |
Deciphering the Relationship Between the Trough Concentration of Posaconazole and Its Efficacy and Safety in Chinese Patients With Hematological Disorders |
title_full |
Deciphering the Relationship Between the Trough Concentration of Posaconazole and Its Efficacy and Safety in Chinese Patients With Hematological Disorders |
title_fullStr |
Deciphering the Relationship Between the Trough Concentration of Posaconazole and Its Efficacy and Safety in Chinese Patients With Hematological Disorders |
title_full_unstemmed |
Deciphering the Relationship Between the Trough Concentration of Posaconazole and Its Efficacy and Safety in Chinese Patients With Hematological Disorders |
title_sort |
deciphering the relationship between the trough concentration of posaconazole and its efficacy and safety in chinese patients with hematological disorders |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2020-10-01 |
description |
Posaconazole (PCZ) is effective in preventing and salvage treatment invasive fungal infections in patients with hematologic disorders. However, PCZ displays highly variable individual pharmacokinetics affecting its efficacy and safety. To investigate the correlation between PCZ concentration and efficacy and safety, the following key influencing factors were explored. A total of 285 trough plasma concentrations (Cmin) of 81 Chinese patients receiving PCZ oral suspension for prophylaxis or treatment of invasive fungal infections were collected in this study. The relationships between Cmin values and clinical response and hepatotoxicity were investigated as well as the incidence of clinical response under different Cmin values of PCZ with a logistic regression model. The concentration of PCZ showed remarkable differences among patients with haematologic disorders. PCZ Cmin values of 0.76 and 1.0 µg/mL were both associated with an over 80% probability of successful response to prophylaxis and treatment of fungal infections, respectively. No association between Cmin values and hepatotoxicity was noted (P > 0.05). Gender, albumin, and co-administration of proton pump inhibitor (PPI) were identified as independent factors influencing PCZ Cmin by multiple linear regression analysis. Furthermore, patients’ C-reactive protein (CRP), albumin, and co-administration of PPI exhibited significant effects on the therapeutic window of patients receiving PCZ for prophylaxis. The plasma concentration is closely associated with therapeutic efficacy of PCZ. It is necessary to adjust the dosing regimens based on PCZ Cmin to obtain an optimal therapeutic response. |
topic |
posaconazole invasive fungal infection pharmacokinetics drug monitoring hematological disorders |
url |
https://www.frontiersin.org/article/10.3389/fphar.2020.575463/full |
work_keys_str_mv |
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