Therapeutic Drug Monitoring最新文献

{"title":"Lamotrigine Use in Lactating Women: Passage into Breast Milk and Infant Exposure: Grand Round/A Case Study.","authors":"Daphne den Besten-Bertholee, Ilse Wegner, Daan J Touw, Peter G J Horst, Paola Mian","doi":"10.1097/FTD.0000000000001299","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001299","url":null,"abstract":"<p><strong>Background: </strong>Lamotrigine, an antiseizure medication used for epilepsy and bipolar disorders, is often prescribed to women of childbearing age due to relatively low teratogenic risk. It is known that lamotrigine use in lactation leads to detectable concentrations in breast milk, although concentrations vary significantly among individuals.</p><p><strong>Case presentation: </strong>A 35-year-old pregnant woman with epilepsy presented to our outpatient clinic. She was seizure-free and was taking lamotrigine 200 mg once daily. She is highly motivated to breastfeed her baby after birth but is concerned about the infant's exposure to lamotrigine through lactation. Lamotrigine concentrations were measured in both the breast milk and plasma of the suckling infants.</p><p><strong>Conclusions: </strong>Although lamotrigine is excreted into breast milk, and detectable in infants, the benefits of breastfeeding should not be overlooked. Higher plasma concentrations generally lead to higher breast milk concentrations, so aiming for the lowest possible maternal plasma levels is beneficial. These findings underscore the importance of TDM in this population.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839787","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":"Determination of 31 Antimicrobials in Human Serum Using Ultra-High Performance Liquid Chromatography With Diode Array Detection for Application in Therapeutic Drug Monitoring.","authors":"Ibrahim El-Haffaf, Mehdi El Hassani, Amélie Marsot","doi":"10.1097/FTD.0000000000001284","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001284","url":null,"abstract":"<p><strong>Background: </strong>A versatile ultra-high performance liquid chromatography method with diode array detection was developed to quantify a wide range of antibiotics in human serum. This method addresses the need for rapid and accurate determination of antibiotic levels to ensure effective patient treatment and support the fight against antibiotic resistance.</p><p><strong>Methods: </strong>This method assesses 31 different compounds covering β-lactams, fluoroquinolones, antifungals, antituberculars, and more. Proteins were precipitated using methanol or acetonitrile, and drugs were extracted by liquid-liquid extraction with dichloromethane. Separation of the antimicrobials was achieved on a pentafluorophenyl column, using a mobile phase of phosphoric acid (0.01 mol/L) and acetonitrile in a gradient elution mode, with a flow rate of 500 μL/min.</p><p><strong>Results: </strong>Almost all compounds were detected at 200 nm. The total analysis time for this method was kept under 18 minutes, including equilibration time.</p><p><strong>Conclusions: </strong>This efficient method enables fast determination of numerous antimicrobial classes, providing clinicians with an essential tool for ensuring effective patient treatment and combating antimicrobial resistance.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847651","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":"Misleading Renal Function Evaluation Leading to Severe Methotrexate-Induced Toxicity.","authors":"Manon Launay, Manon Vogrig, Marlene Damin-Pernik, Hubert Marotte, Sophie Perinel-Ragey","doi":"10.1097/FTD.0000000000001297","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001297","url":null,"abstract":"<p><strong>Abstract: </strong>Low-dose methotrexate has been proposed as therapy for patients with severely disabling psoriasis and psoriatic arthritis. However, it can be associated with severe toxicity, such as pancytopenia, characterized by anemia (hemoglobin level <13 g/dL in men), thrombocytopenia (platelet count <150 × 109/L), and neutropenia or agranulocytosis (neutrophil count <1.5 × 109/L and 0.5 × 109/L, respectively). Here, we report a challenging clinical scenario characterized by pancytopenia and acute renal failure to inform clinicians about potential drug-drug interactions and subclinical renal insufficiency.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839798","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":"An Approach for Improving the Detection and Quantitation of Buprenorphine and Its Metabolites in Maternal and Neonatal Hair.","authors":"Osama Y Alshogran, Wenchen Zhao, Elizabeth E Krans, Steve Caritis, Imam H Shaik, Raman Venkataramanan","doi":"10.1097/FTD.0000000000001291","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001291","url":null,"abstract":"<p><strong>Background: </strong>Buprenorphine (BUP) use is prevalent in pregnant women with opioid use disorder (OUD). Drug monitoring during pregnancy is critical for optimizing dosing regimen and achieving the desired clinical outcomes. Hair can be used as a critical biological matrix for monitoring long-term exposure to drugs. The aim of this study was to optimize the methodology used to quantify BUP and its metabolites in hair samples.</p><p><strong>Methods: </strong>Conditions for hair sample processing (ie, hair washing, incubation temperature, and extraction time) were optimized to maximize extraction recovery. The LC-MS/MS strategy employed here used 4 deuterated internal standards for quantifying BUP and its major metabolites [norbuprenorphine (NBUP), buprenorphine glucuronide (BUP-G), and norbuprenorphine-glucuronide (NBUP-G)] in human hair samples. The optimized conditions were used to measure BUP and its metabolites in hair samples of 5 women undergoing OUD treatment and their neonates.</p><p><strong>Results: </strong>Unwashed hair samples processed by shaking with acetonitrile for 24 hours at 37 °C showed higher BUP (36%) and NBUP (67%) recovery, compared with those processed by incubation at room temperature. The standard curves showed excellent linearity over 0.05-100 ng/mL for BUP and NBUP and 0.1-200 ng/mL for BUP-G and NBUP-G. The assay was partially validated for reproducibility and accuracy and was successfully used for measuring BUP and metabolites in aforementioned hair samples. BUP was identified in all hair samples, while BUP-G was not. BUP was the primary analyte in maternal hair (median: 38.3 pg/mg; 25-75 percentile: 17-152.4 pg/mg), while NBUP-G was predominant in neonatal hair (median: 28.6 pg/mg; 25%-75% percentile: 1.9-112.8 pg/mg).</p><p><strong>Conclusions: </strong>The methodology used for quantifying BUP and its metabolites in hair samples of maternal female patients and their neonates is simple, accurate, and reproducible. The developed method may be useful for measuring fetal exposure to BUP during gestation.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819149","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":"Preliminary Determination of the Therapeutic Reference Range of Lurasidone in Chinese Patients and Analysis of the Factors Influencing Lurasidone Dose-Corrected Concentrations.","authors":"Ye Yang, Zhanzhang Wang, Tao Xiao, Xiaojia Ni, Emei Song, Lijing Dai, Yuqing Chen, Haoyang Lu, Dewei Shang, Yuguan Wen","doi":"10.1097/FTD.0000000000001298","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001298","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study was to determine the therapeutic reference range of lurasidone, and to analyze the factors influencing the dose-corrected concentration of lurasidone in Chinese psychiatric patients, thereby providing a basis for the development of individualized dosing of lurasidone.</p><p><strong>Methods: </strong>A retrospective analysis was conducted for hospitalized patients who had received lurasidone and undergone blood concentration monitoring from May 2022 to September 2023 at the Affiliated Brain Hospital of Guangzhou Medical University. Analyses were based on patient demographic data, treatment regimens, and administered drug concentrations.</p><p><strong>Results: </strong>Data for a total of 123 lurasidone steady-state trough concentrations were collected from 120 hospitalized patients. It was found that 85.56% of lurasidone steady-state trough concentrations were below the lower limit of the lurasidone therapeutic reference range (15 ng·mL-1), and that the median steady-state trough concentration was 7.09 ng·mL-1 (IQ1-IQ3 = 4.12-11.82 ng·mL-1). Gender, age, and co-medication with valproic acid were found to be significant factors influencing lurasidone steady-state trough concentration/daily dose (C/D) values. C/D values for females were 14% higher than those obtained for males. Among patients who did not receive concomitant administration of valproic acid, the C/D values were 55% higher than those who had received co-administered valproic acid. Furthermore, C/D values obtained for elderly patients (≥60 years) were 140% higher than those recorded for adolescents (<18 years) and 157% higher than those in younger adults (18-60 years).</p><p><strong>Conclusions: </strong>The findings of this study indicated that the guideline-recommended therapeutic reference range (15-40 ng·mL-1) for lurasidone may not be appropriate, at least for the Chinese population. More extensive therapeutic drug monitoring is recommended for elderly female patients and those receiving co-medication with lurasidone and valproic acid.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819265","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":"Clinical Efficacy and Safety of Vancomycin Based on Unbound Vancomycin Concentration Monitoring.","authors":"Fefei Ren, Shan Li, Yixin Liu, Xiangchen Li, Xikun Wu, Zhiqing Zhang","doi":"10.1097/FTD.0000000000001292","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001292","url":null,"abstract":"<p><strong>Objective: </strong>To monitor total trough concentration (Cmin_total) and unbound trough concentration (Cmin_free) of vancomycin in clinical samples and analyze the factors influencing them, and to assess their correlation with clinical efficacy and acute kidney injury (AKI).</p><p><strong>Methods: </strong>Plasma samples were processed by protein precipitation, followed by hollow-fiber centrifugal ultrafiltration to separate unbound vancomycin from plasma. Thereafter, Cmin_total and Cmin_free were determined using high-performance liquid chromatography. Clinical data of patients were collected. Factors affecting vancomycin Cmin_total, Cmin_free, and their correlation with clinical efficacy and nephrotoxicity were investigated.</p><p><strong>Results: </strong>A total of 146 samples from 105 included patients were collected. Cmin_total and Cmin_free of vancomycin ranged from 0.62 to 56.08 mcg·mL-1 and 0.61-38.51 mcg·mL-1, respectively. Cmin_total and Cmin_free were correlated (r = 0.8899), influenced by basal creatinine and cystatin C. Higher level of Cmin_free (˃8.6 mcg·mL-1) and nephrotoxic drugs concomitant were risk factors of vancomycin-associated AKI (P < 0.05); Cmin_total and Cmin_free thresholds of vancomycin-associated AKI were 15.35 and 6.83 mcg·mL-1, respectively.</p><p><strong>Conclusions: </strong>vancomycin Cmin_total and Cmin_free, higher Cmin_total and Cmin_free were correlated and higher concentrations of both may increase the risk of AKI.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808279","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":"Unbound Ceftriaxone Concentrations in Plasma Measured Using Ultrafiltration Versus Equilibrium Dialysis: A Short Communication.","authors":"Matthias Gijsen, Dorian Vanneste, Pieter Annaert, Yves Debaveye, Joost Wauters, Isabel Spriet","doi":"10.1097/FTD.0000000000001294","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001294","url":null,"abstract":"<p><strong>Background: </strong>Ceftriaxone is a first-line beta-lactam antibiotic used in diverse clinical settings. Owing to pharmacokinetic alterations, ceftriaxone therapeutic drug monitoring is currently recommended for patients in the intensive care unit. Ultrafiltration is typically used to measure unbound ceftriaxone concentrations, as it is less costly and time-consuming compared with equilibrium dialysis. However, the reference method, equilibrium dialysis, has not been compared with equilibrium dialysis for ceftriaxone to measure the unbound ceftriaxone concentrations. Therefore, unbound ceftriaxone fractions measured by ultrafiltration versus equilibrium dialysis were compared in patients in the intensive care unit.</p><p><strong>Methods: </strong>Total and unbound ceftriaxone plasma fractions were measured by ultrafiltration (9500g at 37°C for 30 minutes) and equilibrium dialysis (12 kDa, 37°C for 4 hours) in 32 plasma samples from 28 patients who were critically ill collected during a previous prospective pharmacokinetic study. Passing-Bablok regression and Bland-Altman analyses were performed to evaluate the agreements between both methods.</p><p><strong>Results: </strong>The median (range) total ceftriaxone plasma concentration was 108.6 (5.2-233) mg/L. The median unbound concentration measured by equilibrium dialysis and ultrafiltration was 14.5 (0.7-52.9) and 23.3 (0.9-79.2) mg/L, respectively, showing a significant difference. Passing-Bablok regression analysis revealed significant proportional and systematic bias. This result was confirmed by Bland-Altman analysis, with a mean relative bias of 43.3% and wide agreement limits (-21% to 108%).</p><p><strong>Conclusions: </strong>Ultrafiltration substantially overestimates the unbound ceftriaxone fraction compared with equilibrium dialysis at 37°C. It is important to report methodological details and consider this information when interpreting unbound fractions of ceftriaxone and other drugs. These findings may impact the therapeutic drug monitoring of ceftriaxone.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808280","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":"Dose Optimization of Amikacin in the Emergency Department: A Population Pharmacokinetics Simulation Study.","authors":"Nada Dia, Sabrina De Winter, Matthias Gijsen, Stefanie Desmet, Peter Vanbrabant, Willy Peetermans, Isabel Spriet, Erwin Dreesen","doi":"10.1097/FTD.0000000000001279","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001279","url":null,"abstract":"<p><strong>Background: </strong>In adult patients with sepsis or septic shock admitted to the emergency department, a single intravenous 15 mg/kg amikacin dose provides inadequate pharmacokinetic-pharmacodynamic target attainment at the locally reported minimum inhibitory concentration (MIC) of 2 mg/L and the European Committee on Antimicrobial Susceptibility Testing clinical breakpoint for Enterobacterales of 8 mg/L.</p><p><strong>Objectives: </strong>To provide an amikacin dosing strategy with a clinically acceptable probability of target attainment (PTA) for all patients.</p><p><strong>Methods: </strong>Stochastic simulations were performed using a two-compartment population pharmacokinetics model of amikacin (NONMEM 7.5). PTA was evaluated for various dosing strategies across a range of virtual patients' body weight, body mass index, serum total protein, serum sodium, fluid balance, and estimated glomerular filtration rate according to the Chronic Kidney Disease Epidemiology Collaboration equation (eGFRCKD-EPI), at the locally reported MIC of 2 mg/L and the clinical breakpoint of 8 mg/L. The pharmacokinetic-pharmacodynamic targets were a 24-hour area under the concentration-time curve (AUC24h)/MIC of ≥80 and a 24-hour postdose concentration (C24h) of < 3 mg/L for efficacy and safety, respectively.</p><p><strong>Results: </strong>The PTA for the clinical breakpoint of 8 mg/L was <90% with standard 15 mg/kg dosing, across all patient characteristics. A flat 1500-mg dose achieved ≥90% PTA for the entire population at a MIC of 2 mg/L. However, at the clinical breakpoint of 8 mg/L, a flat 3500-mg dose provided ≥90% PTA only when the eGFRCKD-EPI was <96 mL/min/1.73 m2. The C24h was similar for 1500 mg and 15 mg/kg dosing, whereas 3500 mg resulted in a higher C24h.</p><p><strong>Conclusions: </strong>A flat dose is recommended over weight-based dosing. However, selecting a 1500-mg or 3500-mg dose may compromise either efficacy (MIC 2 mg/L) or safety (clinical breakpoint 8 mg/L), posing a dilemma. Clinical validation is warranted.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772639","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":"Therapeutic Drug Monitoring of Nirmatrelvir/Ritonavir (Paxlovid) in Patients Treated for COVID-19: Results from a Prospective Multicenter Observational Study.","authors":"Corinna R Böger, Jens Martens-Lobenhoffer, Hans Worthmann, Dirk O Stichtenoth, Torben Brod","doi":"10.1097/FTD.0000000000001290","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001290","url":null,"abstract":"<p><strong>Background: </strong>Paxlovid is a combination of the antiviral agents nirmatrelvir and ritonavir indicated for the oral treatment of high-risk, symptomatic patients with coronavirus disease 2019 (COVID-19). As real-world data on the plasma concentrations of nirmatrelvir/ritonavir (Paxlovid) are limited, the aim of this study was to investigate nirmatrelvir/ritonavir plasma trough levels in a clinical setting using therapeutic drug monitoring.</p><p><strong>Methods: </strong>A prospective, noninterventional, multicenter, observational clinical study was conducted in which the plasma trough levels of nirmatrelvir/ritonavir were simultaneously determined by using liquid chromatography tandem mass spectrometry in patients with symptomatic COVID-19. The blood samples were collected on days 1, 3, and 5 after the first full-dose day (day 0), and patient data such as sex, height, weight, renal function, liver enzymes, and concomitant (co-) medications were obtained to describe the plasma levels with respect to potential influencing factors.</p><p><strong>Results: </strong>A total of 46 blood samples from 21 patients were analyzed. The geometric mean Cmin was 4997 ng/mL for nirmatrelvir and 529.4 ng/mL for ritonavir. The plasma concentrations covered a wide range, the highest being observed in patients with advanced age and renally excreted comedications. Patients older than 65 years had a significantly higher risk of achieving excessive plasma trough concentrations above 8840 ng/mL for nirmatrelvir and 1440 ng/mL for ritonavir compared with younger patients (odds ratio 11.2, 95% confidence interval 1.04-120.4).</p><p><strong>Conclusions: </strong>The plasma trough concentrations of nirmatrelvir and ritonavir in patients treated for symptomatic COVID-19 were higher than the reference values of 2210 ng/mL for nirmatrelvir and 360 ng/mL for ritonavir stated in the product characteristics. Advanced age and renally eliminated comedication were identified as possible influencing factors that warrant further investigation.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771981","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":"Relationships Between Tacrolimus Exposure and Adverse Events in Renal Transplant Patients: The ExpoTac Study.","authors":"Caroline Monchaud, Antoine Humeau, Sabrina Crépin, Lama Kawsarani, Claire Villeneuve, Isabelle Etienne, Jean-Philippe Rerolle, Pierre Marquet","doi":"10.1097/FTD.0000000000001287","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001287","url":null,"abstract":"<p><strong>Abstract: </strong>In transplantation, the association of tacrolimus exposure with efficacy is better known than with adverse effects. The ExpoTac study explored the relationships between tacrolimus exposure and adverse events (AEs) in kidney transplant patients who benefited from at least 3 measurements of tacrolimus area under the curve (AUC) within 2 years of transplantation. The relationships between tacrolimus AUC, trough concentration C0, peak concentration Cmax, and AEs were explored using univariate analysis and Cox models in 386 patients (1281 sets of exposure biomarkers). Headaches and renal impairment potentially induced by tacrolimus were associated with significantly lower mean dose-standardized exposure biomarkers and a higher proportion of Cmax values above the median. Patients with tremor displayed significantly higher mean AUC0-24 (343 ± 79 versus 308 ± 63 hours·mcg/L, P = 0.041). Cox analysis revealed a significant association between (1) the time to the first headache report and mean Cmax, mean AUC0-24, and the proportion of Cmax values above the median (hazard ratios [95% confidence interval] = 0.237 [0.007-0.538]; 7.499 [1.508-29.713]; 5.055 [1.577-17.137]) and (2) the time to first renal impairment report and the proportion of C0 values above the median (0.401 [0.098-0.681]). Refining AUC, Cmax, and C0 upper limits would help to refine tacrolimus therapeutic ranges and limit the risks of AEs after kidney transplantation.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772641","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}