Therapeutic Drug Monitoring最新文献

{"title":"Upadacitinib Optimization in a Patient With Protein-Losing Enteropathy Secondary to (Transient) Nonocclusive Mesenteric Ischemia, Idiopathic Myointimal Hyperplasia, and Hemodialysis: Grand Round.","authors":"Johannes A Kroes, Michiel D Voskuil, Erin H Smeijsters, Christina Krikke, Gerard Dijkstra, Daniël J Touw, Marijn C Visschedijk, Paola Mian","doi":"10.1097/FTD.0000000000001326","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001326","url":null,"abstract":"<p><strong>Background: </strong>We report a case of a 19-year-old man with severe total parenteral nutrition-dependent protein-losing enteropathy who was treated with upadacitinib. Treatment was complicated by renal failure requiring hemodialysis and severe diarrhea, which possibly hindered absorption.</p><p><strong>Methods: </strong>Therapeutic drug monitoring (TDM) and pharmacokinetic analyses were compared with published population pharmacokinetic data to determine the dose adjustments for each patient.</p><p><strong>Results: </strong>Based on TDM results, the dose was gradually increased from 30 mg once daily to 45 mg twice daily. Repeated sampling was performed to estimate the area under the curve (AUC)6.5 (402.5 mcg*h/L), which was higher than data reported in the literature (AUC24 525, SD ± 123 mcg*h/L dosing 30 mg extended release once daily). No AUC24 could be calculated because of the absence of concentrations in the descending part of the concentration-time curve. Clinical improvement was achieved at a higher dose, and no major signs and/or symptoms of drug-related toxicity occurred.</p><p><strong>Conclusions: </strong>Although TDM for Janus-kinase inhibitors is not yet a part of current clinical practice, in this case, the measurement of upadacitinib serum concentrations aided individualized dosing based on TDM.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143781214","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":"External Evaluation of Population Pharmacokinetic Models of Ustekinumab in Patients with Inflammatory Bowel Disease.","authors":"Carles Iniesta-Navalón, Manuel Ríos Saorín, Juan Manuel Neira-Torrecillas, Lorena Rentero-Redondo, Irene Garcia-Masegosa, José Gil-Almela, Elena Urbieta-Sanz","doi":"10.1097/FTD.0000000000001329","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001329","url":null,"abstract":"<p><strong>Background: </strong>Population pharmacokinetic (popPK) models are essential tools for optimizing ustekinumab (UST) dosing for the treatment of inflammatory bowel disease (IBD) through therapeutic drug monitoring. The external validation of these models is necessary to ensure their predictive performance and clinical utility. The aim of the study was to externally validate 4 published popPK models of UST in a real-world cohort of patients with IBD using prediction-based and simulation-based diagnostics, as well as Bayesian forecasting.</p><p><strong>Methods: </strong>Four popPK models of UST, identified through a systematic literature review, were evaluated using data from 99 patients with IBD and 374 serum UST concentrations. Predictive performance and Bayesian forecasting were assessed using statistical metrics, including mean prediction error, median prediction error (MDPE), and median absolute prediction error (MADPE). The acceptability criteria (MDPE ±20%, MADPE ≤30%, F20 ≥35%, and F30 ≥50%) were applied.</p><p><strong>Results: </strong>None of the models satisfied the predefined acceptability criteria. The Xu et al model demonstrated the best performance, achieving an MDPE of 19.55% and the lowest RMSPE (2.88 mcg/mL), but F20 (20.1%) and F30 (32.4%) values fell below thresholds. The model proposed by Adedokun et al showed strong results in simulation-based diagnostics, with only 5.6% of the observed concentrations outside the prediction interval.</p><p><strong>Conclusions: </strong>The models developed by Xu et al and Adedokun et al exhibited the most promising predictive performance and potential clinical applicability for model-informed precision dosing. Refinements to these models and further research are required to enhance their use in personalized UST therapies for IBD.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773355","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":"The Case of Dolutegravir Plus Darunavir Antiretroviral Regimens: Is It Always Useful to Double the Drug Doses?","authors":"Dario Cattaneo, Anna Lisa Ridolfo, Andrea Giacomelli, Antonella Castagna, Alberto Dolci, Spinello Antinori, Cristina Gervasoni","doi":"10.1097/FTD.0000000000001259","DOIUrl":"10.1097/FTD.0000000000001259","url":null,"abstract":"<p><strong>Background: </strong>Antiretroviral drug combinations affect dolutegravir trough concentrations. Here, the authors focused on dolutegravir plus booster darunavir antiretroviral regimens to investigate the effect of the booster and/or timing of drug administration on dolutegravir and darunavir plasma trough concentrations.</p><p><strong>Methods: </strong>This retrospective observational study included consecutive people with HIV (PWH) receiving dolutegravir plus booster darunavir antiretroviral regimens for at least 3 months, with at least one assessment of dolutegravir and darunavir plasma trough concentrations.</p><p><strong>Results: </strong>A total of 200 drug therapeutic drug monitoring results from 116 PWH were included. Dolutegravir and darunavir trough concentrations ranged, respectively, from 70 to 3648 mcg/L and from 102 to 11,876 mcg/L. The antiretroviral drug combination associated with the highest dolutegravir trough concentration was dolutegravir plus darunavir/cobicistat, both once daily (1410 ± 788 mcg/L), whereas dolutegravir once daily plus darunavir/ritonavir twice daily had the lowest trough concentrations (686 ± 481 mcg/L). Doubling the dose of dolutegravir did not significantly increase drug trough concentrations compared with that of once-daily regimens. Instead, the highest darunavir trough concentrations were with ritonavir (2850 ± 1456 mcg/L, P < 0.05 versus cobicistat-based regimens). Doubling the drug dose resulted in a significant increase in the darunavir trough concentration (4445 ± 2926 mcg/L, P < 0.05).</p><p><strong>Conclusions: </strong>Dolutegravir trough concentrations were significantly reduced in PWH receiving darunavir/ritonavir twice daily. This evidence should be carefully considered in clinical conditions requiring higher dolutegravir exposure, such as in the presence of drug-drug interactions with drugs known to reduce dolutegravir bioavailability or in highly experienced PWH.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"309-312"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133835","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":"How to Determine a Therapeutic Reference Range for a Psychotropic Drug Systematically? Recommendations of the TDM Task Force of the AGNP.","authors":"Xenia M Hart, Friederike Amann, Pierre Baumann, Ursula Havemann-Reinecke, Georgios Schoretsanitis, Werner Steimer, Stefan Unterecker, Gerald Zernig, Gerhard Gründer, Christoph Hiemke","doi":"10.1097/FTD.0000000000001264","DOIUrl":"10.1097/FTD.0000000000001264","url":null,"abstract":"<p><strong>Background: </strong>Therapeutic drug monitoring (TDM) is essential for controlling pharmacogenetic and pharmacokinetic variations and for optimizing pharmacotherapy. However, its value is often underestimated because of nonsystematic recommendations for target ranges in the literature. The purpose of this study was to emphasize transparency and systematization in the forthcoming Updates to the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP)-TDM Consensus Guidelines.</p><p><strong>Methods: </strong>Here, a stepwise method for determining therapeutic reference ranges (TRRs) in psychiatry is introduced. By using various data types, a multidimensional approach for establishing a range is presented. The data types were classified based on how effectively they supported the target ranges. This method was demonstrated for 3 drugs commonly used in psychiatry (aripiprazole, olanzapine, and escitalopram).</p><p><strong>Results: </strong>Despite the methodological shortcomings in published concentration-effect studies, the approach used here enabled the determination of reference ranges by combining multiple types of data. The lower limit of the TRR is ideally derived from studies that link blood drug concentrations to clinical effectiveness, particularly symptom-specific responses, after fixed-dose treatment. The upper limit depends on the concentrations associated with adverse reactions or maximal response. Thresholds can be estimated using receiver operating characteristic analyses. Preliminary thresholds were derived from responder concentration data or from expected drug concentrations under approved doses. Positron emission tomography studies were used to further validate these ranges.</p><p><strong>Conclusions: </strong>This study proposed a new standard for determining the TRR of psychotropic drugs, thereby enhancing their clinical utility and validity. Adjusting blood levels to these ranges should improve response rates and medication tolerance.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"199-210"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415275","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":"Ciprofloxacin Dosage Optimization in Cystic Fibrosis Through Therapeutic Drug Monitoring.","authors":"Hamza Sayadi, Yeleen Fromage, Caroline Monchaud, Jeanne Languepin, Alexandra Masson-Rouchaud, Marc Labriffe, Jean-Baptiste Woillard","doi":"10.1097/FTD.0000000000001267","DOIUrl":"10.1097/FTD.0000000000001267","url":null,"abstract":"<p><strong>Background: </strong>Ciprofloxacin (CIP) is effective against many Gram-negative pathogens and penetrates well into respiratory secretions and pulmonary tissues, thus making it useful for treating respiratory infections in patients with cystic fibrosis (CF).</p><p><strong>Methods: </strong>A 13-year-old patient with severe CF and an acute respiratory exacerbation from multidrug-resistant Pseudomonas aeruginosa was treated with 700 mg of CIP every 8 hours. Bronchial secretions confirmed that P. aeruginosa was sensitive to high doses of CIP. Pharmacokinetic monitoring using 2 blood samples estimated the AUC24 at 50 hours*mg/L. This led to an increase in CIP dosage to 850 mg three time a day (TID), then to 1000 mg TID, and finally to 1200 mg every 6 hours.</p><p><strong>Results: </strong>CIP pharmacokinetics can vary significantly, particularly in patients with CF due to increased clearance, ultimately resulting in shorter half-lives and higher risks of therapeutic failure and resistance. Therapeutic drug monitoring helps when adjusting dosages to maintain effective blood concentrations.</p><p><strong>Conclusions: </strong>This case underscores the role of therapeutic drug monitoring in optimizing CIP dosing for patients with CF and highlights the necessity for close collaboration between clinicians and pharmacologists to ensure effective antibiotic exposure.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"189-192"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399970","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":"Optimizing Cefiderocol Dosing Through Population Pharmacokinetic/Pharmacodynamic Simulation: An Assessment of Drug Cost Reductions.","authors":"Kazutaka Oda, Hirofumi Jono, Hideyuki Saito","doi":"10.1097/FTD.0000000000001240","DOIUrl":"10.1097/FTD.0000000000001240","url":null,"abstract":"<p><strong>Background: </strong>Cefiderocol is a siderophore cephalosporin antibiotic with bactericidal activity against carbapenem-resistant Enterobacterales . However, an efficient dosing strategy is yet to be developed. This study aimed to evaluate efficient lower-dose regimens and estimate potential drug cost reductions.</p><p><strong>Methods: </strong>This simulation study used a virtual population of 10,000 resampled individuals based on a reported population pharmacokinetic model. The target index for maximal bactericidal activity was the time for the unbound cefiderocol concentration to be above the minimum inhibitory concentration (TAM_unbound) of 100%, which was determined using a minimum inhibitory concentration distribution or specific value.</p><p><strong>Results: </strong>The probability of achieving 100% TAM_unbound with the standard, low- (reduced by 1 g or one dose), and extended low- (reduced by 2 g or 2 doses) dose regimens was nearly 100%. The lowest probability of achieving 100% TAM_unbound with the extended low-dose regimen at a creatinine clearance range of 90-120 mL/min was 86.4%. The probability of achieving TAM_unbound of 100% was more than 90% for MIC of ≤0.5 mcg/mL with the extended low-dosing regimen. Furthermore, using an efficient dosing regimen reduced the medical costs over a 10-day treatment period for 10 patients, from $122,826.50 to $62,665.69 $ and ¥12,598,187 $ to ¥5,451,173 in the United States and Japan, respectively.</p><p><strong>Conclusionss: </strong>A lower dosing regimen for cefiderocol could result in substantial reductions in drug costs while still achieving 100% TAM_unbound.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"274-280"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477502","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":"Coadministration of Voriconazole and Rifabutin Can Increase the Risk of Adverse Drug Reactions in Patients With Multiple Infections.","authors":"Yoonjin Kim, Sungyeun Bae, Ki Young Huh, Jong Sun Joo, Jikyo Lee, Sang Hoon Song, Kyung-Sang Yu, In-Jin Jang, Jaeseong Oh","doi":"10.1097/FTD.0000000000001241","DOIUrl":"10.1097/FTD.0000000000001241","url":null,"abstract":"<p><strong>Background: </strong>Coinfection of tuberculosis or nontuberculous mycobacteria and Aspergillus presents a challenge in medication selection because of the pharmacokinetic interactions between rifampin and voriconazole. Some researchers have suggested the use of rifabutin as an alternative to rifampin because of its lower hepatic cytochrome P450 enzyme induction potency despite its contraindication to drug labels. This study presents clinical cases of voriconazole and rifabutin coadministration and their potential risks.</p><p><strong>Methods: </strong>This retrospective study was conducted using clinical data from patients who met the following criteria: (1) admitted to Seoul National University Hospital between July 2014 and August 2023 and (2) concurrently administered rifabutin and voriconazole for more than 5 days.</p><p><strong>Results: </strong>Among the 6 patients analyzed, 4 experienced adverse drug reactions (ADRs). Three patients experienced visual and auditory hallucinations, lower extremity numbness, or delirious behavior. Two patients had prolonged the time from the start of the Q wave to the end of the T wave intervals, and 1 had elevated aspartate aminotransferase and alanine aminotransferase levels. In addition, 2 patients experienced severe nausea, poor oral intake, and weight loss. Despite receiving 1.81-fold the recommended voriconazole dosage, a therapeutic concentration (1.0-5.5 mg/L) was not achieved because of cytochrome P450 induction by rifabutin. However, during septic shock, the voriconazole concentration increased by 13.7- to 36-fold.</p><p><strong>Conclusions: </strong>Concurrent use of rifabutin and voriconazole was associated with ADRs, including the time from the start of the Q wave to the end of the T wave prolongation, hallucinations, and severe nausea. Moreover, initially, there was a significant decrease in voriconazole concentrations; however, these concentrations substantially increased during septic shock. Therefore, it is essential to monitor drug concentrations and ADRs during concurrent use of voriconazole and rifabutin.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"303-308"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141634615","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":"Bridging the Gap: Advancing Pharmacogenetic Testing Through Comprehensive Implementation and Evaluation Strategies.","authors":"Sara Rogers, Patrick J Silva, Kenneth Ramos","doi":"10.1097/FTD.0000000000001314","DOIUrl":"10.1097/FTD.0000000000001314","url":null,"abstract":"","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"185-188"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493628","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":"A Refined Population Pharmacokinetic Model-Based Guideline for Individualized PEGasparaginase Dosing in Pediatric Acute Lymphoblastic Leukemia.","authors":"Leiah J Brigitha, Karen Zaky, Rob Pieters, Inge M van der Sluis","doi":"10.1097/FTD.0000000000001252","DOIUrl":"10.1097/FTD.0000000000001252","url":null,"abstract":"<p><strong>Background: </strong>In the Dutch Childhood Oncology Group ALL11 protocol, PEGasparaginase dosing was individualized for standard-risk and medium-risk patients with acute lymphoblastic leukemia. After using our pragmatic old guideline, we aimed to improve individualized PEGasparaginase dosing by developing a population pharmacokinetic model-based dosing guideline.</p><p><strong>Method: </strong>After the 3 doses of 1500 IU/m 2 administered in induction, standard-risk patients received 1 individualized dose and medium-risk patients 14, targeting trough activity levels between 100 and 250 IU/L. The effectiveness, adherence, and toxicity of our new dosing guideline was assessed and compared with the old guideline.</p><p><strong>Results: </strong>In total, 92 patients (714 samples) were included in the new dosing group and 509 patients (4539 samples) were included in the old dosing group. Comparing the effectiveness, we found that 32% (22/67) of patients in the new and 13% (47/354) of patients in the old dosing group were within the target range after the first individualized dose ( P < 0.001). Among medium-risk patients, a median of 3 dose reductions was needed to reach and maintain levels within the target range in the new dosing group compared with 5 in the old dosing group ( P < 0.001). With a continuous PEGasparaginase dosing schedule, target trough activity levels were reached after 2 dose reductions in the new group versus 4 in the old dosing group. The adherence to the new guideline was >99%, with 6/714 recommended doses deviating from the guideline. With exception of a lower proportion of patients with increased (≥grade 3) serum alanine transaminase (34% new vs 64% old, P < 0.05) in the new dosing group, toxicity was comparable between guidelines.</p><p><strong>Conclusions: </strong>With the new dosing guideline, fewer dose-reduction steps are necessary to reach and remain within the target. The high adherence rate emphasized its simplicity and practicality, confirming that it can be easily integrated into clinical practice.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"289-296"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976640","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":"Untangling the Exposure-Response Relationship of Allopurinol in the Setting of Chronic Kidney Disease and Diuretic Use: Implications for Dosing.","authors":"Hailemichael Z Hishe, Sophie L Stocker, Lisa K Stamp, Nicola Dalbeth, Tony R Merriman, Daniel F B Wright","doi":"10.1097/FTD.0000000000001265","DOIUrl":"10.1097/FTD.0000000000001265","url":null,"abstract":"<p><strong>Background: </strong>Allopurinol dose reduction proportional to creatinine clearance (CLcr) results in suboptimal urate lowering in patients with gout. Similarly, diuretic therapy reduces oxypurinol clearance but is unexpectedly associated with the need for higher allopurinol doses to achieve the serum urate target (<0.36 mmol/L). The authors aimed to clarify the relationship between oxypurinol exposure and urate-lowering response in patients with gout at different stages of chronic kidney disease and those taking diuretics to determine the implications for maintenance dose selection.</p><p><strong>Methods: </strong>Oxypurinol and urate data from 5 clinical studies were available. Model-derived steady-state oxypurinol areas under the concentration-time curves (AUCss 0-tau ) were estimated using a Bayesian methodology. The observed response metrics included the percentage reduction in urate from baseline and achievement of the target urate level. Exposure-response was explored graphically and using logistic regression. In addition, the influence of chronic kidney disease and diuretic use on the allopurinol dose and oxypurinol AUCss 0-tau requirements to achieve the serum urate target were explored.</p><p><strong>Results: </strong>Data from 258 patients with gout taking allopurinol representing 1288 paired steady-state oxypurinol and serum urate measurements were available. Higher oxypurinol exposure seems to be required for urate-lowering response normalization and achieve the serum urate target in individuals with reduced kidney function and those taking diuretics. However, allopurinol dose requirements were reduced by 2-fold at the extremes of kidney function and unchanged in those taking or not taking diuretics.</p><p><strong>Conclusions: </strong>A lower allopurinol maintenance dose was required in patients with reduced kidney function (CLcr <30 mL/min), but this was not proportional to CLcr. Diuretic therapy did not influence allopurinol dose requirements.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"281-288"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583630","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}