Lin Cheng, Xi You, Xiaowen Wang, Mingjie Yu, Changsheng Jia
{"title":"伏立康唑和伏立康唑 N-氧化物的血浆低浓度在成人患者肝毒性中的作用","authors":"Lin Cheng, Xi You, Xiaowen Wang, Mingjie Yu, Changsheng Jia","doi":"10.2147/DDDT.S475706","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Hepatotoxicity is an important cause of early withdrawal of voriconazole (VCZ). The role of the plasma trough concentration of VCZ (C<sub>0</sub>) in hepatotoxicity is confusion. VCZ N-oxide is the primary metabolite of VCZ in plasma. We investigated the role of VCZ C<sub>0</sub> and plasma trough concentration of VCZ N-oxide (C<sub>N</sub>) in hepatotoxicity in adult patients.</p><p><strong>Materials and methods: </strong>This was a prospective study. VCZ C<sub>0</sub> and C<sub>N</sub> were measured using liquid chromatography-tandem mass spectrometry.</p><p><strong>Results: </strong>In total, 601 VCZ C<sub>0</sub> and C<sub>N</sub> from 376 adult patients were included. The percentage of grade 1 or higher adverse events for ALP, ALT, AST, γ-GT, and TBIL were 35.4%, 21.0%, 30.1%, 56.2%, and 22.2%, respectively. Compared with younger adult patients, elderly patients (≥65 years) had a higher rate of grade 1 or higher adverse events of ALP. In the multivariate analysis, VCZ C<sub>0</sub> was a risk factor for grade 1 or higher adverse events of AST in elderly patients and TBIL in younger adult patients, and VCZ C<sub>N</sub> was a risk factor for grade 1 or higher adverse events of ALT, AST, and TBIL. Results of the receiver operating characteristic curve analysis indicated that when the VCZ C<sub>0</sub> was higher than 4.0 μg/mL, or the VCZ C<sub>N</sub> was lower than 1.7 μg/mL, the incidence of grade 1 or higher adverse events of AST and TBIL increased.</p><p><strong>Conclusion: </strong>VCZ C<sub>0</sub> and C<sub>N</sub> were associated with liver function-related adverse events. Measurement of VCZ C<sub>N</sub> should be considered for VCZ therapeutic drug monitoring.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":null,"pages":null},"PeriodicalIF":4.7000,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11330242/pdf/","citationCount":"0","resultStr":"{\"title\":\"The Role of Plasma Trough Concentration of Voriconazole and Voriconazole N-Oxide in Its Hepatotoxicity in Adult Patients.\",\"authors\":\"Lin Cheng, Xi You, Xiaowen Wang, Mingjie Yu, Changsheng Jia\",\"doi\":\"10.2147/DDDT.S475706\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>Hepatotoxicity is an important cause of early withdrawal of voriconazole (VCZ). The role of the plasma trough concentration of VCZ (C<sub>0</sub>) in hepatotoxicity is confusion. VCZ N-oxide is the primary metabolite of VCZ in plasma. We investigated the role of VCZ C<sub>0</sub> and plasma trough concentration of VCZ N-oxide (C<sub>N</sub>) in hepatotoxicity in adult patients.</p><p><strong>Materials and methods: </strong>This was a prospective study. VCZ C<sub>0</sub> and C<sub>N</sub> were measured using liquid chromatography-tandem mass spectrometry.</p><p><strong>Results: </strong>In total, 601 VCZ C<sub>0</sub> and C<sub>N</sub> from 376 adult patients were included. The percentage of grade 1 or higher adverse events for ALP, ALT, AST, γ-GT, and TBIL were 35.4%, 21.0%, 30.1%, 56.2%, and 22.2%, respectively. Compared with younger adult patients, elderly patients (≥65 years) had a higher rate of grade 1 or higher adverse events of ALP. In the multivariate analysis, VCZ C<sub>0</sub> was a risk factor for grade 1 or higher adverse events of AST in elderly patients and TBIL in younger adult patients, and VCZ C<sub>N</sub> was a risk factor for grade 1 or higher adverse events of ALT, AST, and TBIL. Results of the receiver operating characteristic curve analysis indicated that when the VCZ C<sub>0</sub> was higher than 4.0 μg/mL, or the VCZ C<sub>N</sub> was lower than 1.7 μg/mL, the incidence of grade 1 or higher adverse events of AST and TBIL increased.</p><p><strong>Conclusion: </strong>VCZ C<sub>0</sub> and C<sub>N</sub> were associated with liver function-related adverse events. Measurement of VCZ C<sub>N</sub> should be considered for VCZ therapeutic drug monitoring.</p>\",\"PeriodicalId\":11290,\"journal\":{\"name\":\"Drug Design, Development and Therapy\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2024-08-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11330242/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug Design, Development and Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/DDDT.S475706\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Design, Development and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/DDDT.S475706","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
The Role of Plasma Trough Concentration of Voriconazole and Voriconazole N-Oxide in Its Hepatotoxicity in Adult Patients.
Objective: Hepatotoxicity is an important cause of early withdrawal of voriconazole (VCZ). The role of the plasma trough concentration of VCZ (C0) in hepatotoxicity is confusion. VCZ N-oxide is the primary metabolite of VCZ in plasma. We investigated the role of VCZ C0 and plasma trough concentration of VCZ N-oxide (CN) in hepatotoxicity in adult patients.
Materials and methods: This was a prospective study. VCZ C0 and CN were measured using liquid chromatography-tandem mass spectrometry.
Results: In total, 601 VCZ C0 and CN from 376 adult patients were included. The percentage of grade 1 or higher adverse events for ALP, ALT, AST, γ-GT, and TBIL were 35.4%, 21.0%, 30.1%, 56.2%, and 22.2%, respectively. Compared with younger adult patients, elderly patients (≥65 years) had a higher rate of grade 1 or higher adverse events of ALP. In the multivariate analysis, VCZ C0 was a risk factor for grade 1 or higher adverse events of AST in elderly patients and TBIL in younger adult patients, and VCZ CN was a risk factor for grade 1 or higher adverse events of ALT, AST, and TBIL. Results of the receiver operating characteristic curve analysis indicated that when the VCZ C0 was higher than 4.0 μg/mL, or the VCZ CN was lower than 1.7 μg/mL, the incidence of grade 1 or higher adverse events of AST and TBIL increased.
Conclusion: VCZ C0 and CN were associated with liver function-related adverse events. Measurement of VCZ CN should be considered for VCZ therapeutic drug monitoring.
期刊介绍:
Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications.
The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas.
Specific topics covered by the journal include:
Drug target identification and validation
Phenotypic screening and target deconvolution
Biochemical analyses of drug targets and their pathways
New methods or relevant applications in molecular/drug design and computer-aided drug discovery*
Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes)
Structural or molecular biological studies elucidating molecular recognition processes
Fragment-based drug discovery
Pharmaceutical/red biotechnology
Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products**
Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development
Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing)
Preclinical development studies
Translational animal models
Mechanisms of action and signalling pathways
Toxicology
Gene therapy, cell therapy and immunotherapy
Personalized medicine and pharmacogenomics
Clinical drug evaluation
Patient safety and sustained use of medicines.