{"title":"肺移植术后他克莫司暴露与临床结果的探索性关联:回顾性单中心经验","authors":"Wenwen Du, Xiaoxing Wang, Dan Zhang, Xianbo Zuo","doi":"10.1007/s00228-024-03640-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to investigate the potential impact of tacrolimus (TAC) exposure on clinical outcomes after lung transplantation.</p><p><strong>Methods: </strong>This retrospective observational study enrolled a total of 228 lung transplant recipients. TAC trough levels (C<sub>0</sub>) were collected for 3 intervals: 0-3 months, 3-12 months, and 12-24 months. The intra-patient variability (IPV) was calculated using coefficient of variation. Genotyping of CYP3A5*3 (rs776746) was performed. Patients were further divided into groups based on the C<sub>0</sub> cut-off value of 8 ng/mL and IPV cut-off value of 30%. Cox proportional hazards regression models were used to explore the potential impact of C<sub>0</sub> and IPV on outcomes of interests, including de-novo donor-specific antibodies (dnDSA), chronic lung allograft dysfunction (CLAD) and mortality.</p><p><strong>Results: </strong>The influence of CYP3A5*3 polymorphism was only significant for C<sub>0</sub> and IPV during the first 3 months. Low C<sub>0</sub> (< 8 ng/mL) at 3-12 months increased the risk of dnDSA (hazard ratio [HR] 2.696, 95% confidence interval [CI] 1.046-6.953) and mortality (HR 2.531, 95% CI 1.368-4.685), while High IPV (≥ 30%) during this period was associated with an increased risk of mortality (HR 2.543, 95% CI 1.336-4.839). Patients with Low C<sub>0</sub>/High IPV combination had significantly higher risks for dnDSA (HR 4.381, 95% CI 1.279-15.008) and survival (HR 6.179, 95% CI 2.598-14.698), surpassing the predictive power provided by C<sub>0</sub> or IPV alone.</p><p><strong>Conclusion: </strong>A combination of Low C<sub>0</sub>/High IPV might be considered in categorizing patients towards risk of adverse clinical outcomes following lung transplantation.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exploratory associations of tacrolimus exposure and clinical outcomes after lung transplantation: A retrospective, single center experience.\",\"authors\":\"Wenwen Du, Xiaoxing Wang, Dan Zhang, Xianbo Zuo\",\"doi\":\"10.1007/s00228-024-03640-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>This study aimed to investigate the potential impact of tacrolimus (TAC) exposure on clinical outcomes after lung transplantation.</p><p><strong>Methods: </strong>This retrospective observational study enrolled a total of 228 lung transplant recipients. TAC trough levels (C<sub>0</sub>) were collected for 3 intervals: 0-3 months, 3-12 months, and 12-24 months. The intra-patient variability (IPV) was calculated using coefficient of variation. Genotyping of CYP3A5*3 (rs776746) was performed. Patients were further divided into groups based on the C<sub>0</sub> cut-off value of 8 ng/mL and IPV cut-off value of 30%. Cox proportional hazards regression models were used to explore the potential impact of C<sub>0</sub> and IPV on outcomes of interests, including de-novo donor-specific antibodies (dnDSA), chronic lung allograft dysfunction (CLAD) and mortality.</p><p><strong>Results: </strong>The influence of CYP3A5*3 polymorphism was only significant for C<sub>0</sub> and IPV during the first 3 months. Low C<sub>0</sub> (< 8 ng/mL) at 3-12 months increased the risk of dnDSA (hazard ratio [HR] 2.696, 95% confidence interval [CI] 1.046-6.953) and mortality (HR 2.531, 95% CI 1.368-4.685), while High IPV (≥ 30%) during this period was associated with an increased risk of mortality (HR 2.543, 95% CI 1.336-4.839). Patients with Low C<sub>0</sub>/High IPV combination had significantly higher risks for dnDSA (HR 4.381, 95% CI 1.279-15.008) and survival (HR 6.179, 95% CI 2.598-14.698), surpassing the predictive power provided by C<sub>0</sub> or IPV alone.</p><p><strong>Conclusion: </strong>A combination of Low C<sub>0</sub>/High IPV might be considered in categorizing patients towards risk of adverse clinical outcomes following lung transplantation.</p>\",\"PeriodicalId\":11857,\"journal\":{\"name\":\"European Journal of Clinical Pharmacology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2024-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Clinical Pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00228-024-03640-6\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/2/16 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Clinical Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00228-024-03640-6","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/16 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Exploratory associations of tacrolimus exposure and clinical outcomes after lung transplantation: A retrospective, single center experience.
Purpose: This study aimed to investigate the potential impact of tacrolimus (TAC) exposure on clinical outcomes after lung transplantation.
Methods: This retrospective observational study enrolled a total of 228 lung transplant recipients. TAC trough levels (C0) were collected for 3 intervals: 0-3 months, 3-12 months, and 12-24 months. The intra-patient variability (IPV) was calculated using coefficient of variation. Genotyping of CYP3A5*3 (rs776746) was performed. Patients were further divided into groups based on the C0 cut-off value of 8 ng/mL and IPV cut-off value of 30%. Cox proportional hazards regression models were used to explore the potential impact of C0 and IPV on outcomes of interests, including de-novo donor-specific antibodies (dnDSA), chronic lung allograft dysfunction (CLAD) and mortality.
Results: The influence of CYP3A5*3 polymorphism was only significant for C0 and IPV during the first 3 months. Low C0 (< 8 ng/mL) at 3-12 months increased the risk of dnDSA (hazard ratio [HR] 2.696, 95% confidence interval [CI] 1.046-6.953) and mortality (HR 2.531, 95% CI 1.368-4.685), while High IPV (≥ 30%) during this period was associated with an increased risk of mortality (HR 2.543, 95% CI 1.336-4.839). Patients with Low C0/High IPV combination had significantly higher risks for dnDSA (HR 4.381, 95% CI 1.279-15.008) and survival (HR 6.179, 95% CI 2.598-14.698), surpassing the predictive power provided by C0 or IPV alone.
Conclusion: A combination of Low C0/High IPV might be considered in categorizing patients towards risk of adverse clinical outcomes following lung transplantation.
期刊介绍:
The European Journal of Clinical Pharmacology publishes original papers on all aspects of clinical pharmacology and drug therapy in humans. Manuscripts are welcomed on the following topics: therapeutic trials, pharmacokinetics/pharmacodynamics, pharmacogenetics, drug metabolism, adverse drug reactions, drug interactions, all aspects of drug development, development relating to teaching in clinical pharmacology, pharmacoepidemiology, and matters relating to the rational prescribing and safe use of drugs. Methodological contributions relevant to these topics are also welcomed.
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