European Journal of Clinical Pharmacology最新文献

{"title":"Recommendations for the safe use of direct oral anticoagulants in patients with cirrhosis based on a systematic review of pharmacokinetic, pharmacodynamic and safety data.","authors":"Maaike M E Diesveld, Daniëlle W M Jacobs- Pijnenburg, Rianne A Weersink, Ina Barzel, Joost P H Drenth, Ton Lisman, Herold J Metselaar, Margje H Monster-Simons, Midas B Mulder, Eline Okel, Katja Taxis, Sander D Borgsteede","doi":"10.1007/s00228-024-03648-y","DOIUrl":"10.1007/s00228-024-03648-y","url":null,"abstract":"<p><strong>Purpose: </strong>The popularity of direct oral anticoagulants (DOACs) is increasing among patients with cirrhosis. Cirrhosis has a major impact on the pharmacokinetics of drugs, potentially increasing adverse events. Safe use of drugs in cirrhosis requires a diligent risk-benefit analysis. The aim of this study is to develop practice recommendations for safe use of DOACs in cirrhosis based on a systematic review of pharmacokinetic, pharmacodynamic and safety data.</p><p><strong>Methods: </strong>We conducted a systematic literature search to identify studies on pharmacokinetics, pharmacodynamics and safety of DOACs in cirrhosis. Data were collected and presented in summary tables by severity of cirrhosis using the Child-Turcotte-Pugh (CTP) classification. A multidisciplinary expert panel evaluated the results and classified the DOACs according to safety.</p><p><strong>Results: </strong>Fifty four studies were included. All DOACs were classified as 'no additional risks known' for CTP A. For CTP B, apixaban, dabigatran and edoxaban were classified as 'no additional risks known'. Apixaban and edoxaban showed fewer adverse events in patients with cirrhosis, while dabigatran may be less impacted by severity of cirrhosis based on its pharmacokinetic profile. Rivaroxaban was classified as 'unsafe' in CTP B and C based on significant pharmacokinetic alterations. Due to lack of data, apixaban, dabigatran and edoxaban were classified as 'unknown' for CTP C.</p><p><strong>Conclusion: </strong>DOACs can be used in patients with CTP A cirrhosis, and apixaban, dabigatran and edoxaban can also be used in CTP B. It is recommended to avoid rivaroxaban in CTP B and C. There is insufficient evidence to support safe use of other DOACs in CTP C cirrhosis.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of methods measuring medication adherence in patients with polypharmacy: a longitudinal and patient perspective.","authors":"Laura Mortelmans, Eva Goossens, Marjan De Graef, Jana Van Dingenen, Anne-Marie De Cock, Mirko Petrovic, Patricia van den Bemt, Tinne Dilles","doi":"10.1007/s00228-024-03661-1","DOIUrl":"10.1007/s00228-024-03661-1","url":null,"abstract":"<p><strong>Purpose: </strong>To explore patients' willingness to have medication adherence measured using different methods and evaluate the feasibility and validity of their combination (i.e., pill counts, a medication diary and a questionnaire assessing adherence two months post-discharge).</p><p><strong>Methods: </strong>(1) A cross-sectional evaluation of the willingness of patients with polypharmacy to have their medication adherence measured post-discharge. (2) Medication adherence was monitored during two months using pill counts based on preserved medication packages and a diary in which patients registered their adherence-related problems. During a home visit, the Probabilistic Medication Adherence Scale (ProMAS) and a questionnaire on feasibility were administered.</p><p><strong>Results: </strong>A total of 144 participants completed the questionnaire at discharge. The majority was willing to communicate truthfully about their adherence (97%) and to share adherence-related information with healthcare providers (99%). More participants were willing to preserve medication packages (76%) than to complete a medication diary (67%) during two months. Most participants reported that preserving medication packages (91%), completing the diary (99%) and the ProMAS (99%) were no effort to them. According to the majority of participants (60%), pill counts most accurately reflected medication adherence, followed by the diary (39%) and ProMAS (1%). Medication adherence measured by pill counts correlated significantly with ProMAS scores, but not with the number of diary-reported problems. However, adherence measured by the medication diary and ProMAS correlated significantly.</p><p><strong>Conclusion: </strong>Combining tools for measuring adherence seems feasible and can provide insight into the accordance of patients' actual medication use with their prescribed regimen, but also into problems contributing to non-adherence.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139995932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world characteristics and use patterns of patients treated with vericiguat: A nationwide longitudinal cohort study in Germany.","authors":"Fabian Kerwagen, Christoph Ohlmeier, Thomas Evers, Stefan Herrmann, Inga Bayh, Alexander Michel, Silvia Kruppert, Joanna Wilfer, Rolf Wachter, Michael Böhm, Stefan Störk","doi":"10.1007/s00228-024-03654-0","DOIUrl":"10.1007/s00228-024-03654-0","url":null,"abstract":"<p><strong>Purpose: </strong>Vericiguat reduced clinical endpoints in patients experiencing worsening heart failure in clinical trials, but its implementation outside trials is unclear.</p><p><strong>Methods: </strong>This retrospective analysis of longitudinally collected data was based on the IQVIA™ LRx database, which includes ~ 80% of the prescriptions of the 73 million people covered by the German statutory health insurance.</p><p><strong>Results: </strong>Between September 2021 and December 2022, vericiguat was initiated in 2916 adult patients. Their mean age was 73 ± 13 years and 28% were women. While approximately 70% were uptitrated beyond 2.5 mg, only 36% reached 10 mg. Median time to up-titration from 2.5 mg to 5 mg was 17 (quartiles: 11-33) days, and from 2.5 to 10 mg 37 (25-64) days, respectively. In 87% of the patients, adherence to vericiguat was high as indicated by a medication possession ratio of  ≥ 80%, and 67% of the patients persistently used vericiguat during the first year. Women and older patients reached the maximal dose of 10 mg vericiguat less often and received other substance classes of guideline-recommended therapy (GDMT) less frequently. The proportion of patients receiving four pillars of GDMT increased from 29% before vericiguat initiation to 44% afterwards.</p><p><strong>Conclusion: </strong>In a real-world setting, despite higher age than in clinical trials, adherence and persistence of vericiguat appeared satisfactory across age categories. Initiation of vericiguat was associated with intensification of concomitant GDMT. Nevertheless, barriers to vericiguat up-titration and implementation of other GDMT, applying in particular to women and elderly patients, need to be investigated further.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11098883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140109710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of drug-drug interaction on linezolid pharmacokinetics: A systematic review.","authors":"Qiang Xu, Yanlei Sang, Anna Gao, Lu Li","doi":"10.1007/s00228-024-03652-2","DOIUrl":"10.1007/s00228-024-03652-2","url":null,"abstract":"<p><strong>Objectives: </strong>Linezolid is a commonly used antibiotic in the clinical treatment of gram-positive bacterial infections. The impacts of drug interactions on the pharmacokinetics of linezolid are often overlooked. This manuscript aims to review the medications that affect the pharmacokinetics of linezolid.</p><p><strong>Methods: </strong>In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we queried the PubMed, Embase, and Cochrane Library for publications from database establishment to November 3, 2023, using the search terms: \"Linezolid\" and \"interaction,\" or \"interact,\" or \"drug-drug interaction,\" or \"co-treatment,\" or \"cotreatment,\" or \"combined,\" or \"combination.\"</p><p><strong>Results: </strong>A total of 24 articles were included. Among the reported medication interactions, rifampicin, levothyroxine, venlafaxine, and phenobarbital could reduce the concentration of linezolid; clarithromycin, digoxin, cyclosporine, proton pump inhibitors, and amiodarone could increase the concentration of linezolid, while aztreonam, phenylpropanolamine, dextromethorphan, antioxidant vitamins, and magnesium-containing antacids had no significant effects on linezolid pharmacokinetics. The ratio of mean (ROM) of linezolid AUC in co-treatment with rifampicin to monotherapy was 0.67 (95%CI 0.58-0.77) and 0.63 (95%CI 0.43-0.91), respectively, in 2 studies, and co-treatment with 500 mg clarithromycin to monotherapy was 1.81 (95%CI 1.49-2.13).</p><p><strong>Conclusions: </strong>This systematic review found that numerous drugs have an impact on the pharmacokinetics of linezolid, and the purported main mechanism may be that linezolid is the substrate of P-glycoprotein. In clinical practice, it is prudent to pay attention to the changes in linezolid pharmacokinetics caused by interactions. Conducting therapeutic drug monitoring (TDM) is beneficial to improve efficacy and reduce adverse reactions of linezolid.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139989677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence, characteristics, and risk factors of drug-associated muscle adverse reaction: a retrospective real-world study of inpatients.","authors":"Anqi Zhao, Daihong Guo, Man Zhu, Ao Gao, Peng Li, An Fu","doi":"10.1007/s00228-024-03662-0","DOIUrl":"10.1007/s00228-024-03662-0","url":null,"abstract":"<p><strong>Objective: </strong>To analyze the clinical characteristics, incidence, and distribution of drug-associated muscle adverse reactions (DAMAR) in real-world inpatients, to provide valuable references for clinical medication use.</p><p><strong>Methods: </strong>We conducted an automatic retrospective monitoring of inpatients from May 1, 2022, to April 30, 2023, to collect information on adverse drug reactions (ADR) of patients and conducted subsequent analyses.</p><p><strong>Results: </strong>Among 102,430 hospitalizations, 1106 cases of DAMARs were identified, yielding an incidence of 1.08%, including 125 cases of rhabdomyolysis at an incidence of 0.12%. Seventy-five percent of the patients experienced muscle adverse reactions within 5 days after taking medication, with a median elevated creatine kinase (CK) value of 420.4 IU/L. Risk factors of DAMAR include age ≥ 65, male sex, obesity, hypertension, hepatic and renal insufficiency, and anemia. No significant correlation was observed between the duration of surgery and CK elevation, while the surgical procedure itself had an impact. The 114 drugs associated were predominantly nervous system drugs, anti-infectives for systemic use, and cardiovascular system drugs, with levofloxacin, pregabalin, and parecoxib being the most frequently associated drugs.</p><p><strong>Conclusion: </strong>Healthcare professionals should be vigilant with patients exhibiting the identified risk factors. Monitoring creatine kinase and related indices when using myotoxic drugs is crucial to preventing serious adverse reactions, ultimately preserving patients' quality of life.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140027729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The safety and efficacy of dabrafenib and trametinib in patients with glioma: A systematic review and meta-analysis.","authors":"Mohammad Amin Habibi, Mohammad Sina Mirjani, Muhammad Hussain Ahmadvand, Pouria Delbari, Omid Alasti","doi":"10.1007/s00228-024-03635-3","DOIUrl":"10.1007/s00228-024-03635-3","url":null,"abstract":"<p><strong>Background: </strong>Dabrafenib and trametinib represent targeted therapy options under investigation for treatment of gliomas harboring BRAF V600 mutations. We systematically reviewed the literature and conducted meta-analyses to assess the efficacy and safety of these agents.</p><p><strong>Methods: </strong>PubMed, Embase, and Scopus were searched from inception to September 2023 for studies examining dabrafenib and/or trametinib for gliomas. Outcomes included response rates (ORR, CR, PR), progression rates (PD), 6- and 12-month PFS, adverse events, and dosing modifications. Meta-analyses were conducted using random effect models.</p><p><strong>Results: </strong>Nine studies met the inclusion criteria. Meta-analysis demonstrated overall response rates (ORR) of 50% (95% confidence interval (CI): 35-65%) for low-grade gliomas (LGG) and 40% (95% CI: 29-51%) for high-grade gliomas (HGG). Pooled ORR was 45% (95% CI: 36-54%) for both glioma grades. The complete response rate was 13% (95% CI: 05-27%) for HGG and 5% (95% CI: 1-10%) for both LGG and HGG. Six-month progression-free survival (PFS) rates reached 87% in LGG and 67% in HGG and a pooled 6-month PFS 78% (95% CI: 58-98%), declining at 12 months to 67% and 44%, respectively, with a pooled 12-month PFS 56% (95% CI: 34-79%). Grade 1-4 adverse events occurred in 100% of LGG and 63% of HGG patients.</p><p><strong>Conclusions: </strong>Dabrafenib and trametinib demonstrate promising anti-tumor efficacy in gliomas, particularly low-grade tumors, achieving durable disease stabilization in many patients. However, toxicity significantly limited tolerability. Additional research should further examine efficacy and refine safe administration protocols across glioma subtypes.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population pharmacokinetics of cyclosporine A in pediatric patients with thalassemia undergoing allogeneic hematopoietic stem cell transplantation.","authors":"Rongda Cai, Limin Zhang, Tingqing Wu, Yumei Huang, Jiejiu Lu, Tianmin Huang, Yun Wu, Dongni Wu, Jianying Qi, Lulu Niu, Yang Xiao, Xin Chen, Yongjun Liu, Yilin Luo, Taotao Liu","doi":"10.1007/s00228-024-03641-5","DOIUrl":"10.1007/s00228-024-03641-5","url":null,"abstract":"<p><strong>Purpose: </strong>To establish the population pharmacokinetics (PPK) model of cyclosporine A(CsA) in pediatric patients with thalassemia undergoing allogeneic hematopoietic stem cell transplantation (HSCT), aiming at providing a reference for clinical dose individualization of CsA.</p><p><strong>Methods: </strong>Children with thalassemia who underwent allogeneic HSCT were enrolled retrospectively. The PPK structural model and the random variable model of CsA were established on NONMEN. And goodness of fit plots (GOFs), visual predictive check (VPC), and bootstrap and normalized prediction distribution errors (NPDE) were used to evaluate the final model.</p><p><strong>Results: </strong>A one-compartment model with first-order absorption was employed to fit the base model. A total of 74 pediatric patients and 600 observations of whole blood concentration were included. The final model included weight (WT) in clearance (CL), alongside post-operative day (POD), fluconazole (FLUC), voriconazole (VORI), posaconazole (POSA), and red blood cell count (RBC) significantly. All the model evaluations were passed.</p><p><strong>Conclusion: </strong>In the PPK model based on the pediatric cohort on CsA with thalassemia undergoing allogeneic HSCT, WT, POD, FLUC, VORI, POSA, and RBC were found to be the significant factors influencing CL of CsA. The reliability and robustness of the final model were excellent. It is expected that the PPK model can assist in individualizing dosing strategy clinically.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139702157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ChatGPT for generating multiple-choice questions: Evidence on the use of artificial intelligence in automatic item generation for a rational pharmacotherapy exam.","authors":"Yavuz Selim Kıyak, Özlem Coşkun, Işıl İrem Budakoğlu, Canan Uluoğlu","doi":"10.1007/s00228-024-03649-x","DOIUrl":"10.1007/s00228-024-03649-x","url":null,"abstract":"<p><strong>Purpose: </strong>Artificial intelligence, specifically large language models such as ChatGPT, offers valuable potential benefits in question (item) writing. This study aimed to determine the feasibility of generating case-based multiple-choice questions using ChatGPT in terms of item difficulty and discrimination levels.</p><p><strong>Methods: </strong>This study involved 99 fourth-year medical students who participated in a rational pharmacotherapy clerkship carried out based-on the WHO 6-Step Model. In response to a prompt that we provided, ChatGPT generated ten case-based multiple-choice questions on hypertension. Following an expert panel, two of these multiple-choice questions were incorporated into a medical school exam without making any changes in the questions. Based on the administration of the test, we evaluated their psychometric properties, including item difficulty, item discrimination (point-biserial correlation), and functionality of the options.</p><p><strong>Results: </strong>Both questions exhibited acceptable levels of point-biserial correlation, which is higher than the threshold of 0.30 (0.41 and 0.39). However, one question had three non-functional options (options chosen by fewer than 5% of the exam participants) while the other question had none.</p><p><strong>Conclusions: </strong>The findings showed that the questions can effectively differentiate between students who perform at high and low levels, which also point out the potential of ChatGPT as an artificial intelligence tool in test development. Future studies may use the prompt to generate items in order for enhancing the external validity of the results by gathering data from diverse institutions and settings.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139729297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding hemoglobin contribution to high-dose methotrexate disposition-population pharmacokinetics in pediatric patients with hematological malignancies.","authors":"Biljana Škorić, Marija Jovanović, Miloš Kuzmanović, Branislava Miljković, Katarina Vučićević","doi":"10.1007/s00228-024-03642-4","DOIUrl":"10.1007/s00228-024-03642-4","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of the present study was to develop a population pharmacokinetic model for methotrexate (MTX) during high-dose treatment (HDMTX) in pediatric patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL) and to describe the influence of variability factors.</p><p><strong>Methods: </strong>The study included 50 patients of both sexes (aged 1-18 years) who received 3 or 5 g/m² of HDMTX. A nonlinear mixed effect modeling approach was applied for data analysis. Parameter estimation was performed by first-order conditional estimation method with interaction (FOCEI), whereas stepwise covariate modeling was used to assess variability factors.</p><p><strong>Results: </strong>The final model is a two-compartment model that incorporates the effect of body surface area and the influence of hemoglobin and serum creatinine on MTX clearance (CL). Population pharmacokinetic values for a typical subject were estimated at 5.75 L/h/m² for clearance (CL), 21.3 L/m² for volume of the central compartment (V1), 8.2 L/m² for volume of the peripheral compartment (V2), and 0.087 L/h/m² for intercompartmental clearance (Q). According to the final model, MTX CL decreases with increasing serum creatinine, whereas a positive effect was captured for hemoglobin. A difference of almost 32% in MTX CL was observed among patients' hemoglobin values reported in the study.</p><p><strong>Conclusion: </strong>The developed population pharmacokinetic model can contribute to the therapy optimization during HDMTX in pediatric patients with ALL and NHL. In addition to renal function and body weight, it describes the influence of hemoglobin on CL, allowing better understanding of its contribution to the disposition of HDMTX.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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":"10.1007/s00228-024-03640-6","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 (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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>A combination of Low C₀/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":2.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139740740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}