Therapeutic Drug Monitoring最新文献

{"title":"Pharmacokinetic and Pharmacodynamic Assessment of Valganciclovir in Infants With Congenital Cytomegalovirus Infection.","authors":"Kotaro Itohara, Kazuhiro Yamamoto, Shunsuke Fujinaka, Mari Hashimoto, Naoki Tamura, Yumi Kitahiro, Tomohiro Omura, Kazumichi Fujioka, Ikuko Yano","doi":"10.1097/FTD.0000000000001257","DOIUrl":"10.1097/FTD.0000000000001257","url":null,"abstract":"<p><strong>Background: </strong>Valganciclovir (VGCV) is administered at a dose of 16 mg/kg 2 times daily for 6 months to treat symptomatic congenital cytomegalovirus (CMV) infections. During the treatment period, approximately 20% of the patients developed grade 3 or higher neutropenia. Currently, information on the pharmacokinetics and pharmacodynamics of ganciclovir, an active metabolite of VGCV, in infants is limited. In the current study, the relationship between ganciclovir concentration and neutropenia was investigated, and a population pharmacokinetic (PPK) model of ganciclovir in infants with symptomatic congenital CMV infection was developed.</p><p><strong>Methods: </strong>Japanese infants who were prescribed oral VGCV for symptomatic congenital CMV infections between July 2017 and January 2021 were included. The relationship between the observed trough ganciclovir concentrations and neutrophil counts was examined. PPK analysis was performed to evaluate the covariates affecting the pharmacokinetics of ganciclovir.</p><p><strong>Results: </strong>Twenty-seven ganciclovir serum samples from 8 patients were analyzed. A moderate negative correlation was observed between the observed trough ganciclovir concentration and neutrophil count. PPK model analysis showed that postmenstrual age (PMA) affected the total body clearance of ganciclovir after correcting for the empirical allometric scaling of body weight. Based on PMA and body weight, a nomogram to achieve the target area under the concentration-time curve from 0 to 24 hours of 40-60 mcg·h·mL -1 of ganciclovir was calculated.</p><p><strong>Conclusions: </strong>The relationship between neutrophil count and ganciclovir trough concentration in infants was clarified. The PPK model showed that the dose of VGCV should be reduced in patients with a low PMA to achieve target exposure.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":"47 3","pages":"393-399"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023815","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":"Association of Plasma Cabozantinib Concentration With Treatment Response and Adverse Events in Japanese Patients With Advanced Renal Cell Carcinoma.","authors":"Shinichi Maruyama, Hiroaki Kobayashi, Tatsuru Hiraga, Tadatsugu Anno, Tansei Sanjo, Masashi Arai, Masaru Ishida, Hiroshi Kanno, Masaru Kato","doi":"10.1097/FTD.0000000000001254","DOIUrl":"10.1097/FTD.0000000000001254","url":null,"abstract":"<p><strong>Background: </strong>Cabozantinib is highly effective against advanced renal cell carcinoma (RCC). However, approximately 60% of the patients require a dose reduction due to severe adverse events. Although associations between trough concentrations of cabozantinib and its efficacy and safety have been reported in other countries, reports on Japanese patients are unavailable. Therefore, we investigated the association of cabozantinib trough concentration with therapeutic efficacy and adverse events in Japanese patients with RCC and evaluated the usefulness of therapeutic drug monitoring.</p><p><strong>Methods: </strong>In this prospective observational study, we measured the trough concentrations of cabozantinib in 10 Japanese patients with RCC enrolled between May 2022 and September 2023. The associations of trough concentration with treatment response, as determined by RECIST 1.1, and the occurrence of grade 2 or higher adverse events were assessed.</p><p><strong>Results: </strong>Trough concentration was higher in patients with controlled cancer than in those with progressive cancer (1024 ± 352 versus 457 ± 216 ng/mL, P = 0.035). In addition, patients with grade 2 or higher adverse events showed a significantly higher trough concentration than those without (1560 ± 513 versus 807 ± 319 ng/mL, P = 0.032). In particular, grade 2 or higher dysgeusia, anorexia, fatigue, and dyspepsia significantly correlated with trough concentrations.</p><p><strong>Conclusions: </strong>This is the first clinical study to demonstrate a correlation between cabozantinib trough concentration, therapeutic efficacy, and adverse events in Japanese patients with RCC. The therapeutic drug monitoring of cabozantinib could be useful for improving therapeutic efficacy and avoiding serious adverse events.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"400-406"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112233","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":"Gene Polymorphisms Play an Important Role in the Drug Interaction Between Posaconazole and Tacrolimus in Renal Transplant Patients.","authors":"Nan Hu, Mengmeng Guan, Bin Gu, Xuping Yang, Qing Qian, Di Zhao, Hui Xue, Jingting Jiang","doi":"10.1097/FTD.0000000000001272","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001272","url":null,"abstract":"<p><strong>Background: </strong>Posaconazole (POSA), a second-generation triazole antifungal drug, inhibits CYP3A and P-glycoprotein. Here, the interaction between POSA and tacrolimus (TAC) in patients undergoing early renal transplantation was studied.</p><p><strong>Methods: </strong>Twenty-two renal transplant recipients who received POSA as antifungal therapy were studied. The following indicators were analyzed statistically: the blood concentration (C), dose (D), and concentration-dose ratio (C/D) of TAC before and after introducing POSA; the change of C/D (ΔC/D) after starting POSA; the genotypes of CYP3A5*3, ABCB1 3435, ABCB1 1236, and POR*28; other routine clinical indicators.</p><p><strong>Results: </strong>After starting POSA, the C, D, and C/D values of TAC were 1.29, 0.57, and 2.74 times the original values, respectively. A linear correlation was observed between the plasma levels of POSA and ΔC/D. The CYP3A5*3 gene polymorphism showed a significant impact on C, D, and C/D of TAC; however, it did not affect the ΔC/D. Polymorphism of the ABCB1 3435 gene had a significant effect on ΔC/D, and patients with the CC genotype in ABCB1 3435 had significantly lower ΔC/D than the CT/TT patients.</p><p><strong>Conclusions: </strong>In renal transplant patients, considerable interindividual variability was observed in the drug interactions between POSA and TAC. The genotypes of CYP3A5*3 and ABCB1 3435 and the plasma level of POSA had strong impact on the interaction between POSA and TAC.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":"47 3","pages":"330-336"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049576","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":"Evaluating the Accuracy and Clinical Utility of AFIAS-10 Point of Care Versus Enzyme-Linked Immunosorbent Assay in Therapeutic Drug Monitoring of Infliximab and Adalimumab.","authors":"Carles Iniesta-Navalón, Manuel Ríos-Saorín, Rebeca Añez-Castaño, Lorena Rentero-Redondo, Patricia Ortíz-Fernandez, Elena Marín-Armero Martínez, Elena Urbieta-Sanz","doi":"10.1097/FTD.0000000000001269","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001269","url":null,"abstract":"<p><strong>Background: </strong>New point-of-care (POC) techniques offer rapid results and address some of the limitations of traditional enzyme-linked immunosorbent assay (ELISA) methods, such as lengthy processing times and delays in therapeutic decision making. It is crucial to evaluate the comparability of POC assays with established ELISA methods to ensure accuracy and reliability in therapeutic drug monitoring. This study aimed to evaluate the analytical performance and clinical utility of the AFIAS-10 POC assay compared with the Promonitor ELISA for quantifying serum concentrations of infliximab (IFX) and adalimumab (ADA) and detecting antidrug antibodies (ATIs and ATAs).</p><p><strong>Methods: </strong>A prospective study was conducted from October 2023 to April 2024, including 225 samples from patients with immune-mediated diseases. The samples were analyzed using both AFIAS-10 POC and Promonitor ELISA assays. To assess the agreement between the 2 methods in terms of quantification, Bland-Altman analysis was performed by examining the mean difference and establishing limits of agreement.</p><p><strong>Results: </strong>The Pearson correlation coefficient indicated strong correlations for IFX (r = 0.932) and ADA (r = 0.967) between the 2 assays. The mean difference between POC and ELISA for IFX was -0.78 mcg/mL and for ADA was 1.54 mcg/mL, respectively. The POC assay tended to underestimate IFX concentrations and overestimate ADA concentrations compared with ELISA.</p><p><strong>Conclusions: </strong>The AFIAS-10 POC assay demonstrated good correlation and concordance with the ELISA method for the quantification of IFX and ADA, as well as for detecting anti-IFX and anti-ADA antibodies. However, this correlation was notably lower at higher drug concentrations.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":"47 3","pages":"346-352"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027138","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":"Lacosamide Pharmacokinetics and Retention in Japanese Patients With Epilepsy: A Retrospective Study on the Influence of Age, Comedications, and Cytochrome P450 2C19 Polymorphism.","authors":"Yoshiaki Yamamoto, Yuka Shiratani, Takuji Nishida, Naotaka Usui, Yoshiyuki Kagawa, Yukitoshi Takahashi, Katsumi Imai","doi":"10.1097/FTD.0000000000001278","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001278","url":null,"abstract":"<p><strong>Background: </strong>This retrospective study aimed to identify the genetic and nongenetic factors that influence serum lacosamide (LCM) concentrations and evaluate the effects of cytochrome P450 2C19 (CYP2C19) polymorphism on the long-term retention rate of LCM.</p><p><strong>Methods: </strong>We analyzed serum samples from 1901 Japanese patients with epilepsy and compared the concentration-to-dose (CD) ratio of LCM among 4 age groups (preschool children, 1-5 years; primary school children, 6-11 years; adolescents, 12-17 years; and adults, ≥18 years). In addition, we performed CYP2C19 genotyping using real-time polymerase chain reaction in 302 patients and classified them into 3 groups: extensive metabolizers (EM: CYP2C19*1/*1), intermediate metabolizers (IM: CYP2C19*1/*2 or *1/*3), and poor metabolizers (PM: CYP2C19*2/*2, *3/*3, or *2/*3). We compared the LCM retention rates between the non-PM (EM and IM) and PM groups using the Kaplan-Meier method.</p><p><strong>Results: </strong>The adult group had the highest mean CD ratio, which was 33.7%, 21.9%, and 7.3% higher than that of preschool children, school children, and adolescents, respectively. The use of enzyme-inducing antiseizure medications (ASMs; ie, phenytoin, phenobarbital, or carbamazepine) reduced the CD ratio by 34.0% in preschool children, 27.3% in primary school children, 24.3% in adolescents, and 27.4% in adults. In adults, the mean CD ratios were 17.7% and 49.0% higher in the IM and PM groups, respectively, than in the EM group. The 3-year retention rate of LCM was higher in the non-PM group than in the PM group (881 vs. 728 days; log-rank test, P < 0.05).</p><p><strong>Conclusions: </strong>Age and the concomitant use of enzyme-inducing ASMs influence LCM pharmacokinetics. In addition, patients with the PM phenotype have a high LCM CD ratio, which may decrease treatment retention. Therapeutic drug monitoring for LCM is a clinically useful method for evaluating pharmacokinetics in individual patients and optimizing the dose of LCM.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":"47 3","pages":"407-412"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000268","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":"Precision Dosing of Intravenous Tocilizumab: Development of Pharmacokinetic Model-Derived Tapering Strategies for Patients With Rheumatoid Arthritis.","authors":"Femke Hooijberg, Stefan P H van den Berg, Zohra Layegh, Maureen Leeuw, Ori Elkayam, Annick de Vries, Mike Nurmohamed, Theo Rispens, Thomas P C Dorlo, Gertjan Wolbink","doi":"10.1097/FTD.0000000000001258","DOIUrl":"10.1097/FTD.0000000000001258","url":null,"abstract":"<p><strong>Background: </strong>Tocilizumab targets the interleukin-6 receptor, and dosing is complex owing to its nonlinear clearance related to target binding. Therefore, tapering tocilizumab requires a different approach than that of tumor necrosis factor inhibitors (TNFi). This study aimed to identify these differences and enable personalized treatment of rheumatoid arthritis (RA) beyond TNFi therapy.</p><p><strong>Methods: </strong>A population pharmacokinetic model of intravenous tocilizumab was developed using data from a randomized controlled trial of dose tapering in patients with RA. Subsequent population-level Monte Carlo and individual Bayesian simulations were performed to create tapering strategies involving dose reduction and interval extension. The target trough concentration of tocilizumab was 5 mg/L. Finally, the drug savings were compared between the 2 methods.</p><p><strong>Results: </strong>The pharmacokinetic of tocilizumab was described with a 2-compartment model with parallel linear (CL 0.20 L/d) and nonlinear (V M 5.2 mg/d, K M 0.19 mg/L) elimination. The linear clearance rate and central volume of distribution increased with lean body mass, and men exhibited higher clearance rates than women. The simulated concentration-time profiles demonstrated that, owing to nonlinear clearance, drug concentrations decreased more than dose-proportionally with lower doses. Tapering based on an individual Bayesian approach emerged as the most promising strategy, yielding a 39% reduction in drug use across virtual populations.</p><p><strong>Conclusions: </strong>Tapering strategies were developed for intravenous tocilizumab, offering potential application in patients with RA who have reached low disease activity or remission, pending clinical validation. The developed strategies demonstrate that the tapering of tocilizumab should be approached more carefully and in smaller steps than that of TNFi.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"337-345"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605620","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":"Examining Different Methods to Assess Busulfan Exposure in Pediatric Hematopoietic Stem Cell Transplant Recipients.","authors":"Maxwell Thompson, Christine E Staatz, Christopher J Fraser, Stefanie Hennig, Rachael Lawson","doi":"10.1097/FTD.0000000000001304","DOIUrl":"10.1097/FTD.0000000000001304","url":null,"abstract":"<p><strong>Background: </strong>Noncompartmental analysis (NCA) and model-based method (MBM) can be used to estimate the cumulative area under the concentration-time curve (AUC cum ) during therapeutic drug monitoring. Understanding predictive differences among these techniques should assist in switching between them and interpreting their results. The aim of this study was to compare busulfan AUC cum prediction based on NCA technique (Kinetica) and MBM (NextDose) applied to the same concentration-time data from pediatric hematopoietic stem cell transplant (HSCT) recipients.</p><p><strong>Methods: </strong>Data on busulfan therapy administered once daily through intermittent infusion were obtained from 4 hospitals in Australia and New Zealand. Busulfan concentrations were measured at 3, 3.25, 4, 5, 6, and 8 hours after infusion initiation over 4 treatment days. Information on busulfan dose, pharmacokinetic profile, and patient covariate factors (if required) were supplied sequentially to Kinetica and NextDose to generate NCA-based and MBM-based predictions of busulfan exposure; differences in AUC cum estimates at the end of the treatment course were compared using Bland-Altman plots, box plots, and Wilcoxon signed-rank sum test.</p><p><strong>Results: </strong>Data from 90 HSCT recipients (2131 busulfan samples) were included. The median patient age and weight were 4.3 years and 17.0 kg, respectively. Median AUC cum estimated based on NCA and MBM were 78.0 mg.h/L [range: 51.7-107.0] and 85.5 mg.h/L [range: 60.6-120.8], respectively, with statistically significant difference in AUC cum values ( P < 0.001). The mean percentage difference in AUC cum values between the 2 different methods suggested that if the AUC cum target using MBMs (NextDose) is 78-101 mg.h/L, then an equivalent target using NCA (Kinetica) would be reduced by 9.1%.</p><p><strong>Conclusions: </strong>When switching between NCA and MBMs to estimate busulfan AUC cum in pediatric HSCT recipients, a change in the target AUC cum is likely required to maintain a similar drug exposure during therapeutic drug monitoring.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"421-426"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441962","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":"Comparative Analysis of 2 Commercially Available Assays for Therapeutic Drug Monitoring of Infliximab and Adalimumab.","authors":"Juan López Pérez, Mercedes Inda-Landaluce, Mercedes Nocito-Colón, Luis Martínez-Lostao","doi":"10.1097/FTD.0000000000001295","DOIUrl":"10.1097/FTD.0000000000001295","url":null,"abstract":"<p><strong>Background: </strong>Tumor necrosis factor is a crucial proinflammatory cytokine in immune-mediated diseases. Tumor necrosis factor inhibitors (TNFi), such as infliximab and adalimumab, effectively treat rheumatological and digestive disorders. However, challenges such as primary nonresponse, secondary treatment failure, or adverse reactions limit their efficacy. Monitoring TNFi levels is essential for optimizing treatment and improving outcomes. An enzyme-linked immunosorbent assay (ELISA; Promonitor) was compared with 2 commercially available methods for quantifying infliximab and adalimumab levels: the chemiluminescence assay (i-Track10) and fluorescence assay (Afias-10).</p><p><strong>Methods: </strong>Serum samples from 166 patients with inflammatory bowel disease were analyzed. Drug levels were measured using i-Track10, Afias-10, and Promonitor. Spearman's correlation analysis, Bland-Altman analysis, analysis of differences, Passing-Bablok regression, and Cohen kappa for agreement assessment were used for statistical analysis.</p><p><strong>Results: </strong>Strong correlations were observed between Promonitor and Afias-10 for infliximab (rs = 0.982) and adalimumab (rs = 0.972), and with i-Track10 (rs = 0.935 for infliximab, rs = 0.947 for adalimumab). However, significant differences indicated noninterchangeability with ELISA. Passing-Bablok regression showed systematic and proportional biases. Cohen kappa exhibited higher concordance with Afias-10 for therapeutic ranges (κ = 0.962 for infliximab, κ = 0.849 for adalimumab) compared with i-Track10.</p><p><strong>Conclusions: </strong>Afias-10 and i-Track10 are suitable for TNFi monitoring but are not interchangeable with ELISA. Consistent assay methods should be used for patient monitoring to ensure accuracy and reliability.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"433-437"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delayed Drug-Drug Interaction Between Antiviral Drugs and Tacrolimus in a Pancreatic Islet Transplant Recipient With SARS-CoV-2 Pneumonia.","authors":"Amelia-Naomi Sabo, Sibylle Cunat, Véronique Kemmel","doi":"10.1097/FTD.0000000000001306","DOIUrl":"10.1097/FTD.0000000000001306","url":null,"abstract":"<p><strong>Background: </strong>PAXLOVID (nirmatrelvir and ritonavir) and VEKLURY (remdesivir) are the first- and second-line antivirals administered to adult patients at risk of severe forms of SARS-CoV-2 infection (COVID-19), such as transplant recipients. As this specific population requires lifelong immunosuppressive treatments, the administration of antivirals with cytochrome P450-modulating properties exposes patients to a high risk of drug-drug interactions (DDI).</p><p><strong>Case presentation: </strong>A 72-year-old male patient who underwent a pancreatic islet transplant experienced DDI between antiviral treatment and tacrolimus during the management of SARS-CoV-2 pneumonia. The patient received a single dose of nirmatelvir/ritonavir followed by a single dose of remdesivir. Tacrolimus treatment was interrupted for the duration of the antiviral treatment, and the concentration of tacrolimus was within the target range for this patient. Once antiviral treatment was stopped, tacrolimus was reintroduced at the initial dose. On day 6, the patient presented with clinical and biological parameters consistent with a tacrolimus overdose. A trough concentration 18 times higher than the therapeutic target was found, prompting tacrolimus to be discontinued for 9 days and reintroduced at a lower dose, followed by a gradual increase based on therapeutic drug monitoring to the initial dose. Clinical and biological parameters gradually returned to baseline levels.</p><p><strong>Conclusions: </strong>Management of DDI between tacrolimus and anti-SARS-CoV-2 drugs requires a substantial therapeutic intervention and close therapeutic drug monitoring during and for several days after antiviral treatment.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"326-329"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liquid Chromatography-Tandem Mass Spectrometry Method for Therapeutic Drug Monitoring of Dalbavancin in Plasma of Pediatric and Young Adult Patients.","authors":"Alessia Cafaro, Marcello Mariani, Federica Pigliasco, Giammarco Baiardi, Sebastiano Barco, Margherita Biondi, Alessio Mesini, Chiara Russo, Carolina Saffioti, Francesca Mattioli, Elio Castagnola, Giuliana Cangemi","doi":"10.1097/FTD.0000000000001260","DOIUrl":"10.1097/FTD.0000000000001260","url":null,"abstract":"<p><strong>Background: </strong>Dalbavancin, an antimicrobial lipoglycopeptide, is authorized in Europe for treating acute bacterial infections of the skin and skin structures in adults and pediatric patients aged 3 months and older. However, off-label dosing regimens have been proposed for various indications beyond acute bacterial infections of the skin and skin structures. This study presents a novel bioanalytical method using liquid chromatography-tandem mass spectrometry to quantify dalbavancin in low-volume plasma samples (50 μL).</p><p><strong>Methods: </strong>The method underwent validation in accordance with international guidelines for bioanalytical method validation and was applied to 9 clinical samples obtained from pediatric and young adult patients undergoing dalbavancin therapy. Liquid chromatography-tandem mass spectrometry analyses were conducted at the G. Gaslini Institute in Genoa, Italy, utilizing an Ultimate 3000 ultra high performance liquid chromatography system coupled to a TSQ Quantiva Triple Quadrupole system (Thermo Fisher Scientific, Milan, Italy). The analytical procedure involved the addition of deuterated dalbavancin as internal standard and a rapid extraction from 50 µL of human plasma, followed by chromatographic separation on a Thermo Scientific Accucore Polar Premium column. Accurate quantification of the analyte was achieved through multiple reaction monitoring detection.</p><p><strong>Results: </strong>The assay exhibited linearity within the concentration range of 0.66-400 mcg/mL in plasma, demonstrating accuracy and reproducibility in the absence of matrix effects. Stability testing was conducted on both quality controls and real samples to establish a robust protocol under real-life conditions.</p><p><strong>Conclusions: </strong>This fast and reliable dalbavancin quantitation method could improve current pediatric clinical practice by enabling data collection for future dose recommendations in special patient populations.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"363-369"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508528","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}