Therapeutic Drug Monitoring最新文献

{"title":"\"Goofballing\": An Emerging Threat With Clinical Challenges.","authors":"Guillaume Drevin, Marie Briet, Séverine Ferec, Chadi Abbara","doi":"10.1097/FTD.0000000000001354","DOIUrl":"10.1097/FTD.0000000000001354","url":null,"abstract":"<p><strong>Background: </strong>The coinjection of methamphetamine and opioids, known as \"goofballing,\" is an emerging practice among people who inject drugs. This combination poses significant clinical challenges due to the opposing pharmacological effects of stimulants and depressants. The increasing prevalence of this practice, particularly in North America, raises significant concerns regarding its impact on public health and patient management.</p><p><strong>Material and methods: </strong>The authors report the case of a 48-year-old man admitted to the intensive care unit with suspected sepsis after intravenous heroin use. During methadone substitution therapy, the patient developed hyperthermia, diffuse myalgia, and mild somnolence. Physical investigation revealed no evidence of infection. Toxicological analyses were conducted on blood and urine samples using targeted and nontargeted screening methods.</p><p><strong>Results: </strong>Toxicological analyses revealed the presence of methamphetamine, amphetamine (a metabolite of methamphetamine), morphine, codeine, methadone, and EDDP in both blood and urine. The presence of 6-acetylmorphine in the urine confirmed recent heroin exposure. No other substances were detected in any sample. The patient was later treated for coinjection of heroin and methamphetamine, which supported the diagnosis of goofballing-induced hyperthermia rather than sepsis.</p><p><strong>Conclusions: </strong>This case highlights the diagnostic challenges associated with the \"goofball\" phenomenon. The coadministration of methamphetamine and heroin can lead to severe atypical toxicological symptoms. Health care providers should be aware of this emerging practice to ensure rapid diagnosis and appropriate management. Public health initiatives should focus on harm reduction strategies to mitigate associated risks.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"691-695"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333926","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":"Impact of UGT1A4 Polymorphisms on the Posaconazole Serum Trough Concentrations in Patients With Acute Myeloid Leukemia Receiving Delayed-Release Tablets.","authors":"François Parant, Marie-Claude Gagnieu, Laurie Di-Pilla, Alexandre Deloire, Anaëlle Joassard, Aurélien Millet, David Barthélémy, Léa Payen, Sophie Ducastelle-Lepretre","doi":"10.1097/FTD.0000000000001319","DOIUrl":"10.1097/FTD.0000000000001319","url":null,"abstract":"<p><strong>Background: </strong>Posaconazole (PCZ) is recommended for antifungal prophylaxis in neutropenic patients with acute myeloid leukemia (AML). Although the delayed-release (DR) tablet of PCZ has better bioavailability than the oral suspension, the serum target trough concentrations of PCZ are not achieved in all patients. Because the metabolism of PCZ is mainly mediated by uridine diphosphate glucuronosyltransferase 1A4 (UGT1A4), we investigated whether UGT1A4 polymorphisms affect PCZ exposure.</p><p><strong>Methods: </strong>This single-center prospective cohort study included 88 adult patients with AML undergoing myelosuppressive chemotherapy and receiving PCZ prophylaxis with DR tablets. PCZ and PCZ-glucuronide concentrations were measured on days 3, 7, 14, and 21 after chemotherapy initiation using liquid chromatography-tandem mass spectrometry. The patients were genotyped for UGT1A4 polymorphisms using high-throughput sequencing. Logistic regression tested the association between suboptimal PCZ concentrations defined as median PCZ concentrations below 0.5 mg/L during the prophylaxis course and the 2 common UGT1A4 polymorphisms: UGT1A4 (c.70C>A) and UGT1A4 (c.142T>G) (referred to as UGT1A4*2 and *3 , respectively).</p><p><strong>Results: </strong>Suboptimal PCZ concentrations were common despite treatment with PCZ DR tablets in induction chemotherapy: 13/88 (15%) and consolidation chemotherapy: 6/28 (21%). An increased risk of suboptimal PCZ concentrations was significantly associated with younger age ( P = 0.029), male sex ( P = 0.034), and presence of the UGT1A4*3 haplotype ( P = 0.031). In addition, patients with the UGT1A4*3 haplotype tended to have higher metabolite-to-parent drug ratios than noncarriers ( P = 0.069).</p><p><strong>Conclusions: </strong>The UGT1A4*3 polymorphism independently contributed to the risk of suboptimal PCZ concentrations in patients with AML taking DR tablets.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"609-618"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568218","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":"Advances in Population Pharmacokinetics of Monoclonal Antibody Drugs.","authors":"Shouhua Mu, Xiaojing Zhang, Jingyan Jin, Yinlian Tong, JieLong Sun, Rong Wang, Wenbin Li","doi":"10.1097/FTD.0000000000001374","DOIUrl":"10.1097/FTD.0000000000001374","url":null,"abstract":"<p><strong>Background: </strong>Monoclonal antibody (mAb) drugs have become an important pillar of modern pharmaceutical fields. Owing to their high specificity and affinity, these drugs have shown broad application prospects in various fields, such as tumor therapy and autoimmune diseases. However, the pharmacokinetic profiles of mAbs are characterized by large individual differences that seriously affect drug efficacy and safety. Therefore, individualized drug delivery and therapeutic drug monitoring are key issues that must be addressed. Population pharmacokinetic (PPK) models contribute to therapeutic drug monitoring and provide a reference for individualized drug administration. Accordingly, the aim of this study was to review current PPK studies on mAb drugs and provide a reference for the clinical individualization of such drugs.</p><p><strong>Methods: </strong>PubMed and China Knowledge Network were searched for relevant original research articles published between 2017 and 2024, and 30 articles were selected for a detailed review based on their titles and abstracts. These included 15 articles in the final analysis, whereas other relevant articles were selected from the reference list.</p><p><strong>Results: </strong>Among these 15 studies, 6 optimized the dosing regimen using the established PPK model, 6 studies only established the PPK model and require further pharmacodynamic studies to optimize the dosing regimen, and 2 studies are currently in the clinical trial phase of the drug.</p><p><strong>Conclusions: </strong>This review of advances in PPK studies of mAb drugs reviews current PPK studies on mAb drugs to inform the clinical individualization of such drugs.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"565-575"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970213","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":"Predictive Performance of Bayesian Dosing Software for Vancomycin in Intensive Care Unit Patients.","authors":"Gali Bai, Hui Qi, Yaqun Huang, Jiao Zhang, Huiying Zhao, Ruiting Wen, Xiaohong Zhang","doi":"10.1097/FTD.0000000000001310","DOIUrl":"10.1097/FTD.0000000000001310","url":null,"abstract":"<p><strong>Background: </strong>According to the updated guidelines, Bayesian-derived area under the curve estimation is recommended to guide vancomycin dosing. However, the Bayesian dosing software that facilitates this procedure has not been adequately assessed in intensive care unit (ICU) patients. This study evaluated the performance of 3 commonly used Bayesian software programs in predicting vancomycin concentrations in ICU patients before they could be utilized for personalized dosing in this population.</p><p><strong>Methods: </strong>Retrospective data from adult ICU patients who were administered vancomycin intravenously were obtained to predict serum concentrations a priori (based solely on patient characteristics) or a posteriori (Bayesian forecasting using measured concentrations). The predictive performance was evaluated via bias and precision using relative bias (rBias) and relative root mean squared error, respectively.</p><p><strong>Results: </strong>Data from 139 patients with 284 vancomycin concentrations were evaluated using 3 software programs: SmartDose (He model), Pharmado (Yasuhara model), and PrecisePK (Rodvald and Goti model). All 3 programs showed clinically acceptable bias with the exception of the Goti model of PrecisePK in an a priori estimation (rBias, 27.44%). A relatively low level of precision in terms of relative root mean squared error was observed in all these programs, but with a marked improvement in the a posteriori estimation (27.69%-37.64%) compared with the a priori situation (45.12%-68.59%).</p><p><strong>Conclusions: </strong>Bayesian dosing software is a potential tool for vancomycin dose optimization in ICU patients. Patients with different physiological and pathological features may be referred to specific Bayesian programs.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"594-602"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12422620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442037","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":"The Effect of Age on Antipsychotic Serum Concentration in Males and Females: A Study Based on Therapeutic Drug Monitoring Data From 19,926 Patients.","authors":"Vigdis Solhaug, Ragnhild Birkeland Waade, Espen Molden, Elisabet Størset, Gudrun Høiseth, Marit Tveito","doi":"10.1097/FTD.0000000000001309","DOIUrl":"10.1097/FTD.0000000000001309","url":null,"abstract":"<p><strong>Background: </strong>Antipsychotic medications are commonly prescribed for older patients; however, documentation on their safety and efficacy in this population is limited. This study aimed to investigate and compare the effect of age on dose-adjusted serum concentrations of 6 commonly used antipsychotic medications in both sexes.</p><p><strong>Methods: </strong>Patients with serum concentration measurements of amisulpride, aripiprazole, clozapine, olanzapine, risperidone, and zuclopenthixol were retrospectively included from a therapeutic drug monitoring service. The primary outcome measure for each antipsychotic was the dose-adjusted serum concentration (C:D ratio), assessed across groups divided by sex and age (18-49 years, 50-74 years, and ≥75 years). The data were analyzed using linear mixed modeling with restricted maximum likelihood estimation.</p><p><strong>Results: </strong>A total of 19,926 patients (53% male) with 74,194 serum concentration measurements were included. For most antipsychotics, the C:D ratios increased significantly with age, with generally larger differences observed in females compared with males. The largest impact of age was observed for risperidone, where C:D ratios in the age groups 50-74 years and ≥75 years were 20% and 81% higher for males, respectively, compared with the reference group (18-49 years). For females, the C:D ratios were 28% and 92% higher, respectively, compared with females aged 18-49 years (all P < 0.001). The smallest impact of age was observed for aripiprazole, with no significant differences in C:D ratios across age groups for males. For females treated with aripiprazole, C:D ratios were 8% and 28% higher in the 50-74 and ≥75 years age groups, respectively, compared with females aged 18-49 years (both P < 0.001).</p><p><strong>Conclusions: </strong>The age-dependent increase in dose-adjusted serum concentrations among males and females varied across different antipsychotics and was highest for risperidone. These findings emphasize the importance of proper monitoring of antipsychotic use in older adults.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"662-668"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12422601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492534","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":"Can Piperacillin Dose Be Predicted by Renal Function in Intensive Care Unit Patients? Comparison of 3 Different Formulas.","authors":"Sophie Magréault, Takoua Khzouri, Khalil Chaïbi, Dany Goldgran-Toledano, Stéphane Gaudry, Julia Desrez, Yves Cohen, Vincent Jullien","doi":"10.1097/FTD.0000000000001367","DOIUrl":"10.1097/FTD.0000000000001367","url":null,"abstract":"<p><strong>Background: </strong>Although the increased risk of piperacillin underexposure has been previously evidenced in intensive care unit patients with augmented renal clearance, it is still unclear whether the piperacillin dose could be a priori adapted according to renal function in these patients.</p><p><strong>Methods: </strong>Steady-state concentrations (Css) of piperacillin were retrospectively collected from 159 adult intensive care unit patients who received a continuous infusion of piperacillin. Renal function was estimated for each patient using the Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration 2021 formulas. The association between these formulas and the risk of piperacillin underexposure and overexposure (Css <80 and >157 mg/L, respectively) was investigated using receiver operating characteristic curves. The proportion of patients with piperacillin underexposure or overexposure to a 16 g/d regimen and the theoretical daily dose (DPDth) required to obtain a Css of 80 mg/L were calculated for 4 different creatinine clearance groups: 60-90, 90-130, 130-160, and >160 mL/min.</p><p><strong>Results: </strong>Creatinine clearance calculated using the Cockcroft-Gault equation was a slightly better predictor of piperacillin underexposure and overexposure, with cutoff values of 128 and 81 mL/min, respectively. The percentage of patients with underexposure increased from 23% to 88% from the 60 to 90 to the ≥160 mL/min group, whereas the mean DPDth simultaneously increased from 13.9 to 30.8 g/d but with an important interindividual variability.</p><p><strong>Conclusions: </strong>These results support a progressive increase in the daily dose of piperacillin with respect to renal function; however, the important interindividual variability precluded the determination of a robust dosing recommendation, making therapeutic drug monitoring mandatory.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001114","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":"Population Pharmacokinetic Models of Ampicillin-Sulbactam Among Adult Patients with Infectious Diseases: A Systematic Review.","authors":"Mohananasunthari Poornachandran, Sabariah Noor Harun, Teh Sin Yin, Noorfatimah Yahaya, Siti Maisharah Sheikh Ghadzi","doi":"10.1097/FTD.0000000000001380","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001380","url":null,"abstract":"<p><strong>Background: </strong>Ampicillin-sulbactam is the first-line treatment for pneumonia, aspiration pneumonia, and infections caused by Acinetobacter baumannii. Several population pharmacokinetic (PK) studies have evaluated the intravenous administration of ampicillin-sulbactam in adults. This systematic review aimed to compare published PK models and identify covariates influencing ampicillin-sulbactam PKs.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted using PubMed and Scopus from inception to March 2025. Relevant articles from reference lists were also incorporated. This review included all population PK models of ampicillin-sulbactam administered intravenously in adult patients with various health conditions.</p><p><strong>Results: </strong>Five studies were reviewed, using a two-compartment model for ampicillin-sulbactam. The PK profiles of ampicillin and sulbactam were found to be similar, with comparable CL and Vd across all selected studies. Ampicillin clearance ranged from 5.58 to 11.03 L/h, whereas sulbactam clearance ranged from 4.79 to 10.50 L/h. The volume of distribution varied from 11.78 to 19.12 L for ampicillin and from 13.89 to 16.77 L for sulbactam. Interindividual variability of ampicillin-sulbactam PK parameters varied across the included studies. Creatinine clearance (CLcr), serum creatinine (SCr), body surface area, body weight, and heart failure were found to be significant covariates affecting the PK parameters.</p><p><strong>Conclusions: </strong>Ampicillin-sulbactam clearance is primarily influenced by renal function (CLcr and SCr) and disease status. None of the studies performed external validation of the developed PK model. This review highlights the PK variability of ampicillin-sulbactam and the need for further research to refine dosing strategies and improve model reliability for clinical application.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993002","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":"Pharmacogenetics of First-Line Antitubercular Drugs: An Update.","authors":"Alessandra Manca, Andrea Calcagno, Antonio D'Avolio, Jessica Cusato","doi":"10.1097/FTD.0000000000001378","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001378","url":null,"abstract":"<p><strong>Background: </strong>Tuberculosis (TB) treatment relies on a prolonged first-line antibiotic regimen, including isoniazid, rifampicin (RF), ethambutol (EMB), and pyrazinamide.Pharmacogenetics plays a crucial role in optimizing TB treatment by addressing individual variability in drug metabolism and responses. Genetic polymorphisms can significantly affect pharmacokinetics and therapeutic outcomes. The aim of this review was to explore the role of pharmacogenetics in first-line antibiotics used to treat TB.</p><p><strong>Methods: </strong>We reviewed the literature using PubMed, Scopus, Web of Science, and the Cochrane Library, focusing on articles published in the last 10 years (from December 2014 to December 2024) on the pharmacogenetics of first-line anti-TB drugs. Only English-language studies involving human subjects were included, prioritizing those investigating genetic variants that affect drug bioavailability.</p><p><strong>Results: </strong>In this study, 33 manuscripts were included.N-acetyltransferase 2 Single-nucleotide polymorphisms were associated with different isoniazid acetylation rates, which affect toxicity and efficacy. Genetic variations in CYP2E1, GSTM1, and MnSOD also contribute to hepatotoxicity.For RF, variants in SLCO1B1, ABCB1, PXR, CAR, CES1, and CES2 genes were related to variability in drug absorption, metabolism, and clearance, highlighting the need for personalized dosing strategies. Notably, SLCO1B1 rs4149056 polymorphism is associated with decreased OATP1B1 RF transport activity, potentially leading to increased plasma exposure, whereas other polymorphisms modulate drug exposure and clearance rates. In addition, sex, body weight, and genotype influenced RF pharmacokinetics, suggesting the need for tailored dosing recommendations based on patient characteristics.Similarly, variability in EMB pharmacokinetics is associated with CYP1A2 2159, which is related to a 50% reduction in bioavailability, necessitating dose adjustments in patients coinfected with TB and HIV. Some variants of ABCB1, OATP1B1, PXR, VDR, CYP24A1, and CYP27B1 may further modulate the plasma and intracellular concentrations of EMB, thereby influencing drug efficacy.</p><p><strong>Conclusions: </strong>This review highlights the importance of integrating pharmacogenetic insights into clinical practice to enhance the efficacy of TB treatment, minimize toxicity, and prevent drug resistance. Despite promising evidence, further research and clinical validation are required to implement pharmacogenetics in routine TB management. Future advancements in therapeutic drug monitoring and omics technologies will pave the way for precision medicine in TB therapy.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993484","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 and Pharmacogenomics of Thiopurines in Inflammatory Bowel Disease: International Guidelines Revisited.","authors":"Ahmed B Bayoumy, Luc J J Derijks, Nanne K H de Boer","doi":"10.1097/FTD.0000000000001373","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001373","url":null,"abstract":"<p><strong>Background: </strong>Thiopurines, including azathioprine, mercaptopurine, and thioguanine (TG), are widely used as maintenance therapies for inflammatory bowel disease (IBD). However, their clinical utility is challenged by interindividual variability in metabolism, therapeutic response, and toxicity. Therapeutic drug monitoring (TDM) and pharmacogenomics have emerged as critical tools for optimizing thiopurine therapies. This review aimed to compare the international guidelines on TDM and the pharmacogenomics of thiopurines in IBD to identify global differences in TDM practices.</p><p><strong>Methods: </strong>A scoping review was conducted using PubMed, Embase, Web of Science, and official Gastroenterology Society web sites. We identified and analyzed international guidelines for thiopurine TDM and pharmacogenomics, focusing on recommendations for metabolite monitoring, thiopurine methyltransferase, and nudix hydrolase 15 (NUDT15) testing.</p><p><strong>Results: </strong>A total of 23 guidelines from North America, Europe, Africa, Asia, Latin America, and Oceania were included in this study. TDM was recommended in 65% of the guidelines with various approaches; some advocated reactive monitoring (6-TGN and/or 6-MMPR in response to treatment failure or adverse effects), whereas others recommended proactive thiopurine monitoring to prevent toxicity. Thiopurine methyltransferase testing is recommended in 74% of these guidelines, although its relevance has been questioned in Asian populations. NUDT15 testing is mentioned in only 13% of the guidelines, despite its established role in predicting thiopurine-induced myelotoxicity, particularly in Asian and Hispanic populations. Accessibility limitations in low-resource regions have led to a reliance on empirical dose adjustments and complete blood count monitoring.</p><p><strong>Conclusions: </strong>There is substantial variability in the global TDM and pharmacogenomic practices for thiopurines in IBD. Limited recommendations for NUDT15 testing and disparities in resource availability have contributed to inconsistent clinical implementation. Future guidelines should address these gaps by integrating cost-effective pharmacogenomic strategies and incorporating alternative monitoring methods such as DNA-TG for NUDT15 variants. This review highlights the variability in the global recommendations for thiopurine TDM and pharmacogenomics. To optimize thiopurine therapy and reduce toxicity risks, future guidelines should include NUDT15 testing and consider TG, low-dose thiopurine, and allopurinol treatments.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970292","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":"Large-Scale Real-World Monitoring of Mycophenolic Acid Exposure in Liver Transplantation: Impact of Bayesian Dose Adjustment.","authors":"Marc Labriffe, Hamza Sayadi, Jean-Baptiste Woillard, Ludovic Micallef, Franck Saint-Marcoux, Alexandre Destere, Pierre Marquet, Caroline Monchaud","doi":"10.1097/FTD.0000000000001377","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001377","url":null,"abstract":"<p><strong>Background: </strong>Mycophenolate mofetil is widely used in liver transplantation but poses dosing challenges owing to the narrow therapeutic window and high pharmacokinetic variability of its active moiety, mycophenolic acid (MPA). Overexposure increases the risk of adverse effects, whereas underexposure increases the risk of rejection and graft loss. The ImmunoSuppressant Bayesian Dose Adjustment (ISBA) platform estimates the MPA area under the curve (AUC)0-12h using 3 post-dose samples (20 minutes, 1 hour, 3 hours) and provides dose recommendations to target an AUC0-12h of 30-60 mg·h/L. The aim of this study was to describe the MPA AUC0-12h and assess the impact of ISBA-guided dose adjustments.</p><p><strong>Methods: </strong>MPA concentrations were measured at each visit, and AUCs were estimated in real time during routine clinical follow-up. All data collected from liver-transplant recipients aged ≥18 years from October 2005 to May 2020 were retrospectively analyzed. Dosing recommendations were adjusted proportionally to reach the AUC target of 45 mg.h/L.</p><p><strong>Results: </strong>A total of 3632 requests involving 1872 patients were analyzed, making this the largest real-world cohort of this population reported to date. Among them, 658 patients benefited from at least 2 successive dose adjustments, allowing for a comparison between the results obtained without any prior use of the online platform and those obtained after the first visit (AUC of the second visit). At the first visit (before any dose recommendation) during the first year after transplantation, the median AUC0-12h (interquartile range) was 27 (16-39) mg·h/L (n = 422). After dose adjustment recommendation, the median AUC0-12h increased significantly to 38 (30-49) mg·h/L (n = 205, P < 0.001). The proportion of patients within the therapeutic target range (30-60 mg.h/L) increased from 40% to 61% (+21%, P < 0.001).</p><p><strong>Conclusions: </strong>Many patients were underexposed to MPA before dose adjustment. The ISBA recommendations significantly improved target attainment rates.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970281","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}