Therapeutic Drug Monitoring最新文献

{"title":"Serum Concentration of Antidepressant Drugs in Geriatric Day Care Patients With Renal Insufficiency and Multimorbidity.","authors":"Sibylle Reber, Alexandra S Herr, Stefan Unterecker, Maike Scherf-Clavel","doi":"10.1097/FTD.0000000000001285","DOIUrl":"10.1097/FTD.0000000000001285","url":null,"abstract":"<p><strong>Background: </strong>Geriatric depression is challenging to treat owing to age-related changes in pharmacokinetics and comorbidities. Although renal insufficiency and multimorbidity are typical geriatric complications that cannot be completely separated from each other, no study has examined the influence of these factors on the serum concentrations of antidepressants. For the first time, we evaluated the effects of these factors in combination on the dose-corrected serum concentration (C/D) of antidepressants in geriatric patients.</p><p><strong>Methods: </strong>In this retrospective study, data from 123 geriatric patients in a gerontopsychiatric day care unit at the University Hospital of Würzburg were analyzed. Multiple linear regression analysis and analysis of variance with confounders were used to examine the associations between glomerular filtration rate (GFR) and stages of renal impairment and the C/D of venlafaxine, mirtazapine, sertraline, and escitalopram corrected for multimorbidity, sex, lithium intake, and the number of triple whammy drugs.</p><p><strong>Results: </strong>GFR ( P < 0.001, ß = -0.070) was associated with the C/D of the active moiety of venlafaxine (N = 32). GFR, multimorbidity, and sex were not associated with the C/D of mirtazapine, escitalopram, or sertraline.</p><p><strong>Conclusions: </strong>As the influence of sex may be less pronounced than that of decreasing GFR in terms of the C/D of the active moiety of venlafaxine in geriatric patients, we recommend considering the GFR for dose adjustment rather than sex. In conclusion, even in patients with mild renal impairment, serum venlafaxine concentration should be monitored to prevent overdosing. Mirtazapine, sertraline, and escitalopram may be well-suited antidepressants for geriatric patients with renal function impairment stage 2-3 as well as multimorbidity.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"297-302"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717183","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":"Model-Informed Dosing Optimization of Tacrolimus for Concomitant Administration With Itraconazole to Japanese Lung Transplant Recipients.","authors":"Ren Takahashi, Kotaro Itohara, Shunsaku Nakagawa, Yoshiki Katada, Mitsuhiro Sugimoto, Keisuke Umemura, Katsuyuki Matsumura, Daiki Hira, Masahiro Tsuda, Yurie Katsube, Satona Tanaka, Akihiro Ohsumi, Daisuke Nakajima, Miki Nagao, Hiroshi Date, Tomohiro Terada","doi":"10.1097/FTD.0000000000001249","DOIUrl":"10.1097/FTD.0000000000001249","url":null,"abstract":"<p><strong>Background: </strong>Tacrolimus is an immunosuppressant administered to patients undergoing lung transplantation. Itraconazole is often concomitantly used with tacrolimus to prevent fungal infections and increase tacrolimus concentration. However, the pharmacokinetics of tacrolimus in Japanese lung transplant recipients and the effect of itraconazole on its pharmacokinetics have not been adequately evaluated. Population pharmacokinetic analysis was conducted to develop an optimal dose adjustment method for use upon itraconazole initiation in Japanese lung transplant recipients.</p><p><strong>Methods: </strong>This study comprised Japanese lung transplant recipients whose blood tacrolimus and itraconazole concentrations were measured between January 2017 and December 2019. A nonlinear mixed-effects modeling program was used to explore the covariates of tacrolimus pharmacokinetics and effects of concomitant itraconazole use. Using the model, the optimal initial tacrolimus dose was calculated and a dose adjustment method comprising concomitant itraconazole use was developed.</p><p><strong>Results: </strong>A total of 1693 tacrolimus trough blood concentrations and 85 itraconazole trough plasma concentrations were obtained from 43 patients. Postoperative day, albumin level, and administration route were extracted as covariates for tacrolimus pharmacokinetics. The drug-drug interaction between tacrolimus and itraconazole could be predicted more accurately by considering the concentration-dependent inhibition of itraconazole. The optimal initial tacrolimus dose was 2.0 mg twice daily for tube and 1.5 mg twice daily for oral administration. To maintain the target concentration, the tacrolimus dose was reduced by 60% upon itraconazole initiation.</p><p><strong>Conclusions: </strong>This study is the first to use population pharmacokinetic analysis to assess the interaction between tacrolimus and itraconazole in patients who underwent lung transplantation. These results provide useful insights for optimizing the initial tacrolimus dose for concomitant itraconazole use.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"248-257"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902946","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 and Evaluation Strategies for Pharmacogenetic Testing in Hospital Settings: A Scoping Review.","authors":"Angela Wu, Edward J Raack, Colin J D Ross, Bruce C Carleton","doi":"10.1097/FTD.0000000000001243","DOIUrl":"10.1097/FTD.0000000000001243","url":null,"abstract":"<p><strong>Background: </strong>Pharmacogenetic testing in clinical settings has improved the safety and efficacy of drug treatment. There is a growing number of studies evaluating pharmacogenetic implementation and identifying barriers and facilitators. However, no review has focused on bridging the gap between identifying barriers and facilitators of testing and the clinical strategies adopted in response. This review was conducted to understand the implementation and evaluation strategies of pharmacogenetic testing programs.</p><p><strong>Methods: </strong>A PRISMA-compliant scoping review was conducted. The included studies discussed pharmacogenetic testing programs implemented in a hospital setting. Quantitative, qualitative, and mixed design methods were included.</p><p><strong>Results: </strong>A total of 232 of the 7043 articles that described clinical pharmacogenetic programs were included. The most common specialties that described pharmacogenetic implementation were psychiatry (26%) and oncology (16%), although many studies described institutional programs implemented across multiple specialties (19%). Different specialties reported different clinical outcomes, but all reported similar program performance indicators, such as test uptake and the number of times the test recommendations were followed. There were benefits and drawbacks to delivering test results through research personnel, pharmacists, and electronic alerts, but active engagement of physicians was necessary for the incorporation of pharmacogenetic results into clinical decision making.</p><p><strong>Conclusions: </strong>Further research is required on the maintenance and sustainability of pharmacogenetic testing initiatives. These findings provide an overview of the implementation and evaluation strategies of different specialties that can be used to improve pharmacogenetic testing.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"211-247"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296135","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":"Midazolam Boosting With Cobicistat in a Patient With Drug-Resistant Epilepsy and Focal Status Epilepticus.","authors":"Tessa van den Born-Bondt, Niels Westra, Katarzyna Krzywicka, Harmen R Moes, Manon Schuls-Fouchier, Daan J Touw, Thijs H Oude Munnink","doi":"10.1097/FTD.0000000000001283","DOIUrl":"10.1097/FTD.0000000000001283","url":null,"abstract":"<p><strong>Background: </strong>This report presents the case of a patient with drug-resistant epilepsy. Despite treatment with 4 antiepileptic drugs, the patient experienced an increasing frequency of focal seizures, necessitating hospitalization, and continuous intravenous midazolam infusion.</p><p><strong>Methods: </strong>Cobicistat was introduced as a pharmacokinetic booster to decrease the metabolic clearance of midazolam, leading to increased exposure and an extended half-life.</p><p><strong>Results: </strong>Cobicistat boosting allowed the switch from intravenous to oral midazolam, and the patient was discharged on an oral midazolam regimen.</p><p><strong>Conclusions: </strong>Cobicistat can be effectively used to boost midazolam exposure pharmacokinetically in patients with drug-resistant epilepsy who require stable midazolam blood concentrations.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"193-195"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11902592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676932","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":"Challenges in Validating Population Pharmacokinetic Models for Clozapine Dosage Prediction and Therapeutic Drug Monitoring.","authors":"Abdul Wasay Sherazi","doi":"10.1097/FTD.0000000000001280","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001280","url":null,"abstract":"","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":"47 2","pages":"313-315"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626153","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 Psychotropic Drugs: What We Know, What We Don't, and the Controversies.","authors":"Olav Spigset","doi":"10.1097/FTD.0000000000001263","DOIUrl":"10.1097/FTD.0000000000001263","url":null,"abstract":"","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"183-184"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583619","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":"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 C min 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":"258-264"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","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":"One Concentration Does Not Fit All: It Is Time to Personalize the Therapeutic Range of Infliximab in Crohn Disease.","authors":"Bénédicte Franck, Camille Tron, Marie-Clémence Verdier, Eric Bellissant, Anne-Sophie Peaucelle, Xavier Roblin, Florian Lemaitre, Guillaume Bouguen","doi":"10.1097/FTD.0000000000001251","DOIUrl":"10.1097/FTD.0000000000001251","url":null,"abstract":"<p><strong>Background: </strong>Therapeutic drug monitoring of infliximab is commonly performed based on trough concentration. However, doses and dosing intervals may be adapted to patient outcomes, and this trough concentration target may correspond to a large range of exposures in terms of the area under the concentration-time curve (AUC). The objectives of this study were to assess the real-life exposure to intravenous infliximab in patients with Crohn disease in remission at year 1 and to assess the evolution of exposure in patients who switched to subcutaneous infliximab.</p><p><strong>Methods: </strong>The authors conducted a retrospective observational pharmacokinetic study in patients with Crohn disease who had available infliximab concentrations during intravenous and subcutaneous infliximab maintenance therapy as per the standard of care. Infliximab exposure parameters (AUCs and trough concentrations, C 0 ) were compared for different dosing regimens of intravenous infliximab before (intravenous) and after (subcutaneous) the switch.</p><p><strong>Results: </strong>A total of 113 patients had 383 intravenous infliximab concentrations. Dosing intervals ranged from 4 to 12 weeks. The median/range/CV% C 0 , AUC 0-t , and AUC 0-8weeks were 5.3 mcg/mL [<LLoQ-49.6]/71.6%, 37,792 mcg.h/mL [4971-116,366]/33.1%, and 41,582 mcg.h/mL [7953-232,048]/43.9%, respectively. Forty-one patients had available paired C 0 after both intravenous and subcutaneous administration. A poor correlation was found between preswitch intravenous infliximab C 0 and postswitch subcutaneous infliximab C 0 .</p><p><strong>Conclusions: </strong>In this study, the authors suggested that in patients treated with IV IFX, different targets of C 0 should be proposed according to treatment schemes and that AUC 0-t might be a relevant determinant of clinical remission. Moreover, exposure did not remain stable throughout the switch from IV to SC IFX in any patient. These variations may depend on the intravenous dosing interval before switching.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"265-273"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772640","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":"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":"196-198"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","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":"Therapeutic Drug Monitoring of Thiopurines in Patients With Inflammatory Bowel Disease: Observations From Daily Practice.","authors":"Mila Lovrić, Kristina Dukić, Silvija Čuković-Čavka, Lana Ganoci, Nada Božina, Vladimir Trkulja","doi":"10.1097/FTD.0000000000001327","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001327","url":null,"abstract":"<p><strong>Background: </strong>Patients with inflammatory bowel disease (IBD) to be treated with thiopurines should undergo preemptive genotyping for reduced-function thiopurine methyltransferase (TPMT) polymorphisms. Therapeutic drug monitoring (TDM) is recommended in cases of toxicity or a lack of efficacy. The relationship between TPMT genotype and 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP) concentrations in the early steady state was assessed.</p><p><strong>Methods: </strong>Consecutive adults with IBD to be treated with azathioprine underwent preemptive TPMT genotyping and were dosed accordingly. All patients underwent TDM after 4-6 weeks of treatment and occasionally thereafter.</p><p><strong>Results: </strong>Of the 235 included patients, 45 were not genotyped for various reasons (45 samples at first TDM, 66 overall). Of the 190 patients who were genotyped, 19 (10%) were heterozygous (*1/*3) (19 samples at first TDM, 32 overall) and 171 (90%) were wild-type (171 samples at first TDM, 280 overall). At first TDM, 7 patients were hypermethylators, and 6 were identified at later TDMs. Compared with patients with a wild-type genotype or those who were not genotyped, those who were heterozygous consistently had markedly higher 6-TGN (2-fold, 3.7-fold if dose-adjusted) and lower 6-MMP (75%-90%, 30%-50% if dose-adjusted) concentrations (pmol/8 × 108 red blood cells). Based on the 6-TGN/6-MMP profiles, they were 2-3 times less likely to be classified as receiving \"too low of a dose\" (6-TGN <235 and 6-MMP <5700 pmol/8 × 108 red blood cells), and 4-20 times more likely to be classified as receiving \"too high of a dose\" (6-TGN >450).</p><p><strong>Conclusions: </strong>These data support the importance of TPMT genotyping and suggest that thiopurine TDM generates supplementary information and should be performed for all patients.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731126","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}