Therapeutic Drug Monitoring最新文献

{"title":"Population Pharmacokinetics of Perampanel in Chinese Pediatric and Adult Patients With Epilepsy.","authors":"Jiayu Yang, Sitian Zhang, Zhigang Zhao, Shenghui Mei, Weixing Feng","doi":"10.1097/FTD.0000000000001296","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001296","url":null,"abstract":"<p><strong>Background: </strong>Perampanel is a promising epilepsy treatment with an innovative mechanism of action. This study was performed to investigate the factors affecting perampanel clearance in a population pharmacokinetic (PPK) model of Chinese pediatric and adult patients with epilepsy.</p><p><strong>Methods: </strong>A total of 135 perampanel plasma concentrations from 125 patients with epilepsy were analyzed using the PPK model with nonlinear mixed-effects modeling. One-compartment and proportional residual models best described the pharmacokinetics of perampanel. Covariate effects on the model parameters were assessed using forward and backward elimination. Goodness-of-fit, bootstrapping, visual predictive checks, and normalized prediction distribution errors were used to evaluate the model. Monte Carlo simulations were conducted to assess the impact of covariate combinations on perampanel plasma concentrations at different dosages.</p><p><strong>Results: </strong>In the final PPK model, body weight (BW), concomitant carbamazepine (CBZ), oxcarbazepine (OXC), and C-reactive protein (CRP) levels significantly influenced perampanel clearance. The interindividual clearance was calculated as follows: 0.84 × (BW/70)0.53 × eCBZ × eOXC × eCRP (CBZ = 0.98, when comedicated with carbamazepine; OXC = 0.43, when comedicated with oxcarbazepine; CRP = -0.69, when CRP >15 mg/L, otherwise = 0). The estimates (relative standard error) for clearance and apparent volume of distribution of the final model were 0.84 L/h (8.75%) and 64.35 L (19.78%), respectively. The model maintained its stability and effectiveness with moderate predictability.</p><p><strong>Conclusions: </strong>BW and CBZ, OXC, and CRP levels may influence perampanel clearance in both pediatric and adult patients with epilepsy according to a population pharmacokinetic model that included real-world data.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delayed Drug-Drug Interaction Between Antiviral Drugs and Tacrolimus in a Pancreatic Islet Transplant Recipient with SARS-CoV-2 Pneumonia-A Case Study.","authors":"Amelia-Naomi Sabo, Sibylle Cunat, Véronique Kemmel","doi":"10.1097/FTD.0000000000001306","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001306","url":null,"abstract":"<p><strong>Background: </strong>PAXLOVID (nirmatrelvir and ritonavir) and VEKLURY (remdesivir) are the first- and second-line antivirals administered to adult patients at risk of severe forms of SARS-CoV-2 infection (COVID-19), such as transplant recipients. As this specific population requires lifelong immunosuppressive treatments, the administration of antivirals with cytochrome P450-modulating properties exposes patients to a high risk of drug-drug interactions (DDI).</p><p><strong>Case presentation: </strong>A 72-year-old male patient who underwent a pancreatic islet transplant experienced DDI between antiviral treatment and tacrolimus during the management of SARS-CoV-2 pneumonia. The patient received a single dose of nirmatelvir/ritonavir followed by a single dose of remdesivir. Tacrolimus treatment was interrupted for the duration of the antiviral treatment, and the concentration of tacrolimus was within the target range for this patient. Once antiviral treatment was stopped, tacrolimus was reintroduced at the initial dose. On day 6, the patient presented with clinical and biological parameters consistent with a tacrolimus overdose. A trough concentration 18 times higher than the therapeutic target was found, prompting tacrolimus to be discontinued for 9 days and reintroduced at a lower dose, followed by a gradual increase based on therapeutic drug monitoring to the initial dose. Clinical and biological parameters gradually returned to baseline levels.</p><p><strong>Conclusions: </strong>Management of DDI between tacrolimus and anti-SARS-CoV-2 drugs requires a substantial therapeutic intervention and close therapeutic drug monitoring during and for several days after antiviral treatment.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Getting Tacrolimus Dosing Right.","authors":"Pierre Marquet","doi":"10.1097/FTD.0000000000001266","DOIUrl":"10.1097/FTD.0000000000001266","url":null,"abstract":"<p><strong>Abstract: </strong>Tacrolimus (TAC) dosing is typically guided by the trough concentration (C0). Yet, significant relationships between TAC C0 and clinical outcomes have seldom been reported or only with adverse events. Large retrospective studies found a moderate correlation between TAC C0 and the area under the curve (AUC), where, for any given C0 value, the AUC varied 3- to 4-fold between patients (and vice versa). However, no randomized controlled trial evaluating the dose adjustment based on TAC AUC has been conducted yet. A few observational studies have shown that the AUC is associated with efficacy and, to a lesser extent, adverse effects. Other studies showed the feasibility of reaching predefined target ranges and reducing underexposure and overexposure. TAC AUC 0-12 h is now most often assessed using Bayesian estimation, but machine learning is a promising approach. Microsampling devices are well accepted by patients and represent a valuable alternative to venous blood sample collection during hospital visits, especially when a limited sampling strategy is required. As AUC monitoring cannot be proposed very frequently, C0 monitoring has to be used in the interim, which has led to fluctuating doses in patients with an AUC/C0 ratio far from the population mean, because of different dose recommendations between the 2 biomarkers. We proposed estimating the individual AUC/C0 ratio and derived individual C0 targets to be used in between or as a replacement for AUC monitoring. Existing technology and evidence are now sufficient to propose AUC monitoring interspersed with individualized-C0 monitoring for all patients with kidney transplants while collecting real-world data to strengthen the evidence.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"41-48"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward Analytical Performance Specifications for Immunosuppressive Drug Quantification in Transplantation: An Opinion Article.","authors":"Maria Shipkova, Eberhard Wieland, Ekkerhard Schütz","doi":"10.1097/FTD.0000000000001261","DOIUrl":"10.1097/FTD.0000000000001261","url":null,"abstract":"<p><strong>Background: </strong>Analytical methods require performance that meets the clinical needs. Different approaches for setting up permissible analytical imprecision goals (pCVA%) for drug analyses have been reported. The aim of this study was to calculate the pCV A % for cyclosporine, tacrolimus, everolimus, sirolimus, and mycophenolic acid using 4 alternative approaches, to compare the results and to critically discuss advantages and disadvantages of each model.</p><p><strong>Methods: </strong>The approaches to evaluate pCV A % were (A) based on biological variation observed in routine measurement results between 2022 and 2023 in the authors' laboratory, (B) derived from the terminal elimination half-life and dosing interval of the drugs, and (C and D) explored from the width of the therapeutic ranges (TR) by the 2 methods. For approach A, routine measurement data for cyclosporine and tacrolimus, obtained through liquid chromatography-tandem mass spectrometry and electrochemiluminescence immunoassays, were evaluated separately.</p><p><strong>Results: </strong>The 4 alternative approaches for deriving pCV A % yielded similar results, for cyclosporine and tacrolimus in an analytical method dependent manner. The average pCV A % was 5.2%, 5.6%, 5.1%, 4.8%, and 7.7% for cyclosporine, tacrolimus, everolimus, sirolimus, and mycophenolic acid, respectively. The most challenging goals were those using TR-related approaches, while those using the biological variation approach were most easily achievable. Approach B resulted in more stringent goals for drugs with longer elimination half-lives (eg, everolimus and sirolimus).</p><p><strong>Conclusions: </strong>There is no single ideal approach for setting goals of drug analysis. However, the pCV A % values derived from the various approaches are similar and confirm that a <6% target proposed by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology is adequate and realistic in combination with state-of-the-art measurement technologies. In the authors' opinion, approaches based on the width of the TR are preferable, as they represent a common basis for clinical decisions and reflect elements of biological variation and analytics used to establish the TR.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"32-40"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alternate Sampling Matrices for Therapeutic Drug Monitoring of Immunosuppressants.","authors":"Benedetta C Sallustio","doi":"10.1097/FTD.0000000000001282","DOIUrl":"10.1097/FTD.0000000000001282","url":null,"abstract":"<p><strong>Background: </strong>Immunosuppressant (IS) therapeutic drug monitoring (TDM) relies on measuring mostly pharmacologically inactive erythrocyte-bound and/or plasma protein-bound drug levels. Variations in hematocrit and plasma protein levels complicate interpretation of blood calcineurin inhibitor (CNI) and inhibitors of the molecular target of rapamycin (mTORi) concentrations. Variable binding of mycophenolic acid (MPA) to albumin similarly complicates its TDM in plasma. A different matrix may improve IS concentration-response relationships and better reflect exposures at sites of action.</p><p><strong>Methods: </strong>This review explores the evidence for IS TDM using peripheral blood mononuclear cell (PBMC), graft tissue, and total or unbound plasma concentrations.</p><p><strong>Results: </strong>Tandem mass spectrometry provides the sensitivity for assessing these matrices. But several challenges must be addressed, including minimizing hemolysis during blood collection, preventing IS efflux during PBMC preparation, and determining the need for further purification of the PBMC fraction. Assessing and reducing nonspecific binding during separation of unbound IS are also necessary, especially for lipophilic CNIs/mTORi. Although TDM using PBMC or unbound plasma concentrations may not be feasible due to increased costs, plasma CNI/mTORi levels may be more easily integrated into routine TDM. However, no validated TDM targets currently exist, and published models to adjust blood CNI/mTORi concentrations for hematocrit or to predict PBMC, and total and unbound plasma IS concentrations have yet to be validated in terms of measured concentrations or prediction of clinical outcomes.</p><p><strong>Conclusions: </strong>Even if CNI/mTORi measurements in novel matrices do not become routine, they may help refine pharmacokinetic-pharmacodynamic relationships and improve mathematical models for TDM using whole blood. Notably, there is evidence to support measuring unbound MPA in patients with severe renal dysfunction, hypoalbuminemia, and hyperbilirubinemia, with some proposed TDM targets.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"105-117"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142732764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Effective Half-Life and Its Impact on Time to Steady State for Oral MeltDose Tacrolimus (LCPT) in De Novo Kidney Transplant Recipients.","authors":"Jeremiah D Momper, Raman Venkataramanan, Arin S Jantz, Diane M Cibrik, Kelly Birdwell, Tk Nguyen, Brian M Masters, Samir J Patel","doi":"10.1097/FTD.0000000000001270","DOIUrl":"10.1097/FTD.0000000000001270","url":null,"abstract":"<p><strong>Background: </strong>For extended-release drug formulations, effective half-life (t 1/2eff ) is a relevant pharmacokinetic parameter to inform dosing strategies and time to reach steady state. Tacrolimus, an immunosuppressant commonly used for the prophylaxis of organ rejection in transplant patients, is available as both immediate- and extended-release formulations. To the best of our knowledge, the t 1/2eff of tacrolimus from these different formulations has not yet been assessed. The objective of this study was to characterize the t 1/2eff and terminal half-life (t 1/2z ) of an extended-release once-daily tacrolimus formulation (LCPT) and twice-daily immediate-release tacrolimus (IR-Tac).</p><p><strong>Methods: </strong>A noncompartmental analysis of pharmacokinetic data obtained from a phase 2 study in de novo kidney transplant recipients receiving either LCPT or IR-Tac was conducted. Intensive blood sampling was performed on days 1, 7, and 14, and tacrolimus whole blood concentrations were measured using a validated liquid chromatography with tandem mass spectrometry method. T 1/2eff was estimated using within-participant accumulation ratios. T 1/2z was estimated by linear regression of the terminal phase of the concentration versus time profile.</p><p><strong>Results: </strong>The median accumulation ratios of LCPT and IR-Tac on day 14 were 3.18 and 2.06, respectively.The median (interquartile range; IQR) t 1/2eff for LCPT at day 14 of dosing was 48.4 (37.4-77.9) hours, whereas the t 1/2z was 20.3 (17.6-22.9) hours. For IR-Tac, the median (IQR) t 1/2eff and t 1/2z on day 14 were 12.5 (8.8-23.0) hours and 12.2 (9.2-15.7) hours, respectively.</p><p><strong>Conclusions: </strong>Consistent with its prolonged release of tacrolimus, LCPT demonstrated a higher accumulation ratio and a longer t 1/2eff compared with IR-Tac. These findings underscore the pharmacokinetic differences between different drug formulations of the same moiety and may help inform dose adjustments for LCPT in kidney transplantation.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"169-173"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11702898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Limited Sampling Strategies Fail to Accurately Predict Mycophenolic Acid Area Under the Curve in Kidney Transplant Recipients and the Impact of Enterohepatic Recirculation.","authors":"Moataz E Mohamed, Abdelrahman Saqr, Mahmoud Al-Kofahi, Guillaume Onyeaghala, Rory P Remmel, Christopher Staley, Casey R Dorr, Levi Teigen, Weihua Guan, Henry Madden, Julia Munoz, Duy Vo, Bryan Sanchez, Rasha El-Rifai, William S Oetting, Arthur J Matas, Ajay K Israni, Pamala A Jacobson","doi":"10.1097/FTD.0000000000001248","DOIUrl":"10.1097/FTD.0000000000001248","url":null,"abstract":"<p><strong>Background: </strong>Therapeutic drug monitoring for mycophenolic acid (MPA) is challenging due to difficulties in measuring the area under the curve (AUC). Limited sampling strategies (LSSs) have been developed for MPA therapeutic drug monitoring but come with risk of unacceptable performance. The authors hypothesized that the poor predictive performance of LSSs were due to the variability in MPA enterohepatic recirculation (EHR). This study is the first to evaluate LSSs models performance in the context of EHR.</p><p><strong>Methods: </strong>Adult kidney transplant recipients (n = 84) receiving oral mycophenolate mofetil underwent intensive MPA pharmacokinetic sampling. MPA AUC 0-12hr and EHR were determined. Published MPA LSSs in kidney transplant recipients receiving tacrolimus were evaluated for their predictive performance in estimating AUC 0-12hr in our full cohort and separately in individuals with high and low EHR.</p><p><strong>Results: </strong>None of the evaluated LSS models (n = 12) showed good precision or accuracy in predicting MPA AUC 0-12hr in the full cohort. In the high EHR group, models with late timepoints had better accuracy but low precision, except for 1 model with late timepoints at 6 and 10 hours postdose, which had marginally acceptable precision. For all models, the good guess of predicted AUC 0-12hr (±15% of observed AUC 0-12hr ) was highly variable (range, full cohort = 19%-61.9%; high EHR = 4.5%-65.9%; low EHR = 27.5%-62.5%).</p><p><strong>Conclusions: </strong>The predictive performance of the LSS models varied according to EHR status. Timepoints ≥5 hours postdose in LSS models are essential to capture EHR. Models and strategies that incorporate EHR during development are required to accurately ascertain MPA exposure.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"174-182"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic Boosting of Calcineurin Inhibitors in Transplantation: Pros, Cons, and Perspectives.","authors":"Smita Pattanaik, Caroline Monchaud","doi":"10.1097/FTD.0000000000001288","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001288","url":null,"abstract":"<p><strong>Abstract: </strong>The concept of pharmacokinetic (PK) boosting of calcineurin inhibitors (CNI) emerged after the FDA approval of cyclosporine-A. Several studies followed, and the proof of concept was well established by the late 1990s. This also continued for the next blockbuster immunosuppressant, tacrolimus. The driver for such research was an endeavor to save costs, as both drugs were expensive due to patent protection. Two CYP inhibitors, ketoconazole and diltiazem, have been extensively studied in this context and continue to be prescribed off-label along with the CNI. It has been observed that using ketoconazole reduces the dose requirement of tacrolimus by about 50% and 30% with diltiazem, which is in conformity with their pharmacological actions. Off-label co-prescription of these drugs with CNI is often encountered in low and middle-income countries. The foremost reason cited is economic. This article collates the evidence from the clinical studies that evaluate the PK-boosting effects of CNI and also reviews the gaps in the current evidence base. The current knowledge prevents the transplant community from making meaningful inferences about the risks and benefits of such strategies. Although the PK-boosting strategy can lead to serious adverse events, emerging evidence suggests that it may be advantageous for individuals with high CNI dose requirements. Hence, PK boosting may be an unmet need in the therapeutics of CNI. Nevertheless, there are several unanswered questions surrounding such use, and therefore, this merits testing in well-designed clinical studies. Moreover, drugs with better safer profiles and a history of successful PK boosting may be considered for evaluation with CNI.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":"47 1","pages":"118-140"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implementation of Volumetric Finger-Prick Self-Sampling for Therapeutic Drug Monitoring of Immunosuppressants After Kidney Transplantation: Lessons Learned From the Practice.","authors":"Nils Tore Vethe, Anders Åsberg, Stein Bergan, Ida Robertsen, Karsten Midtvedt","doi":"10.1097/FTD.0000000000001281","DOIUrl":"10.1097/FTD.0000000000001281","url":null,"abstract":"<p><strong>Background: </strong>Home-based hospital services are becoming increasingly popular, and the addition of remote outpatient appointments after kidney transplantation facilitates more practical and closer follow-up. In this context, finger-prick self-sampling is an important aspect of monitoring of immunosuppressants and biomarkers. Nevertheless, several issues must be addressed to ensure the feasibility and quality when implementing microsampling in clinical practice. We summarize our experiences and opinions in this field.</p><p><strong>Methods: </strong>This article is based on the authors' experience regarding the laboratory and clinical implementation of finger-prick self-sampling in kidney transplant recipients. The referenced literature is related to the authors' knowledge in this field.</p><p><strong>Results: </strong>We present considerations for the selection of relevant analytes, key characteristics of selected volumetric sampling tools (Mitra and Capitainer), and the associated sampling pitfalls. In addition, we address the requirements for patients performing finger-prick sampling, appropriate design of methods and workflow, critical points for validation, and aspects related to logistics and digital solutions.</p><p><strong>Conclusions: </strong>Volumetric finger-prick self-sampling is suitable for monitoring immunosuppressants and certain biomarkers that are relevant to outpatient follow-up after kidney transplantation. We believe that a carefully designed system for the entire workflow, including patient training, will be beneficial in enabling a safe experience for transplant recipients, as well as ensuring overall efficiency and adequate quality. In the future, a combination of immunosuppressants with a wide range of biomarkers has significant potential for use in at-home self-sampling after kidney transplantation.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"98-104"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Everolimus Personalized Therapy: Second Consensus Report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.","authors":"Satohiro Masuda, Florian Lemaitre, Markus J Barten, Stein Bergan, Maria Shipkova, Teun van Gelder, Sander Vinks, Eberhard Wieland, Kirsten Bornemann-Kolatzki, Mercè Brunet, Brenda de Winter, Maja-Theresa Dieterlen, Laure Elens, Taihei Ito, Kamisha Johnson-Davis, Pawel K Kunicki, Roland Lawson, Nuria Lloberas, Pierre Marquet, Olga Millan, Tomoyuki Mizuno, Dirk Jan A R Moes, Ofelia Noceti, Michael Oellerich, Smita Pattanaik, Tomasz Pawinski, Christoph Seger, Ron van Schaik, Raman Venkataramanan, Phil Walson, Jean-Baptiste Woillard, Loralie J Langman","doi":"10.1097/FTD.0000000000001250","DOIUrl":"10.1097/FTD.0000000000001250","url":null,"abstract":"<p><strong>Abstract: </strong>The Immunosuppressive Drugs Scientific Committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology established the second consensus report to guide therapeutic drug monitoring (TDM) of everolimus (EVR) and its optimal use in clinical practice 7 years after the first version was published in 2016. This version provides information focused on new developments that have arisen in the last 7 years. For the general aspects of the pharmacology and TDM of EVR that have retained their relevance, readers can refer to the 2016 document. This edition includes new evidence from the literature, focusing on the topics updated during the last 7 years, including indirect pharmacological effects of EVR on the mammalian target of rapamycin complex 2 with the major mechanism of direct inhibition of the mammalian target of rapamycin complex 1. In addition, various concepts and technical options to monitor EVR concentrations, improve analytical performance, and increase the number of options available for immunochemical analytical methods have been included. Only limited new pharmacogenetic information regarding EVR has emerged; however, pharmacometrics and model-informed precision dosing have been constructed using physiological parameters as covariates, including pharmacogenetic information. In clinical settings, EVR is combined with a decreased dose of calcineurin inhibitors, such as tacrolimus and cyclosporine, instead of mycophenolic acid. The literature and recommendations for specific organ transplantations, such as that of the kidneys, liver, heart, and lungs, as well as for oncology and pediatrics have been updated. EVR TDM for pancreatic and islet transplantation has been added to this edition. The pharmacodynamic monitoring of EVR in organ transplantation has also been updated. These updates and additions, along with the previous version of this consensus document, will be helpful to clinicians and researchers treating patients receiving EVR.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"4-31"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}