Therapeutic Drug Monitoring最新文献

{"title":"Model-Informed Precision Dosing of Intravenous Busulfan in Thai Pediatrics Undergoing Hematopoietic Stem Cell Transplantation.","authors":"Apichaya Puangpetch, Fabienne Thomas, Usanarat Anurathapan, Samart Pakakasama, Suradej Hongeng, Jiratha Rachanakul, Santirhat Prommas, Nutthan Nuntharadthanaphong, Étienne Chatelut, Chonlaphat Sukasem, Félicien Le Louedec","doi":"10.1097/FTD.0000000000001225","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001225","url":null,"abstract":"<p><strong>Background: </strong>Conditioning bifunctional agent, busulfan, is commonly used on children before hematopoietic stem cell transplantation. Currently, at the Ramathibodi hospital, Bangkok, Thailand, initial dosing is calculated according to age and body surface area, and 7 samples per day are used for therapeutic drug monitoring (TDM). This study aimed to identify the best strategies for individual dosages a priori from patient characteristics and a posteriori based on TDM.</p><p><strong>Methods: </strong>The pharmacokinetic data set consisted of 2018 plasma concentrations measured in 135 Thai (n = 135) pediatric patients (median age = 8 years) and were analyzed using a population approach.</p><p><strong>Results: </strong>Body weight, presence of malignant disease, and genetic polymorphism of Glutathione S-transferase Alpha-1 (GSTA1) were predictors of clearance. The optimum sampling times for TDM concentration measurements were 0.25, 2, and 5 hours after a 3-hour infusion. This was sufficient to obtain a Bayesian estimate of clearance a posteriori. Simulations showed the poor performance of a priori formula-based dose calculations with 90% of patients demonstrating a 69%-151% exposure interval around the target. This interval shrank to 85%-124% if TDM was carried out only at day 1 and to 90%-116% with TDM at days 1 and 3.</p><p><strong>Conclusions: </strong>This comprehensive study reinforces the interest of TDM in managing interindividual variability in busulfan exposure. Therapeutic drug monitoring can reliably be implemented from 3 samples using the Bayesian approach, preferably over 2 days. If using the latter is not possible, the formulas developed herein could present an alternative in Thai patients.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140959596","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":"Developing Parametric and Nonparametric Models for Model-Informed Precision Dosing: A Quality Improvement Effort in Vancomycin for Patients With Obesity.","authors":"Maria-Stephanie A Hughes, Jasmine H Hughes, Jeffrey Endicott, Meagan Langton, John W Ahern, Ron J Keizer","doi":"10.1097/FTD.0000000000001214","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001214","url":null,"abstract":"<p><strong>Background: </strong>Both parametric and nonparametric methods have been proposed to support model-informed precision dosing (MIPD). However, which approach leads to better models remains uncertain. Using open-source software, these 2 statistical approaches for model development were compared using the pharmacokinetics of vancomycin in a challenging subpopulation of class 3 obesity.</p><p><strong>Methods: </strong>Patients on vancomycin at the University of Vermont Medical Center from November 1, 2021, to February 14, 2023, were entered into the MIPD software. The inclusion criteria were body mass index (BMI) of at least 40 kg/m2 and 1 or more vancomycin levels. A parametric model was created using nlmixr2/NONMEM, and a nonparametric model was created using metrics. Then, a priori and a posteriori predictions were evaluated using the normalized root mean squared error (nRMSE) for precision and the mean percentage error (MPE) for bias. The parametric model was evaluated in a simulated MIPD context using an external validation dataset.</p><p><strong>Results: </strong>In total, 83 patients were included in the model development, with a median age of 56.6 years (range: 24-89 years), and a median BMI of 46.3 kg/m2 (range: 40-70.3 kg/m2). Both parametric and nonparametric models were 2-compartmental, with creatinine clearance and fat-free mass as covariates to c clearance and volume parameters, respectively. The a priori MPE and nRMSE for the parametric versus nonparametric models were -6.3% versus 2.69% and 27.2% versus 30.7%, respectively. The a posteriori MPE and RMSE were 0.16% and 0.84%, and 13.8% and 13.1%. The parametric model matched or outperformed previously published models on an external validation dataset (n = 576 patients).</p><p><strong>Conclusions: </strong>Minimal differences were found in the model structure and predictive error between the parametric and nonparametric approaches for modeling vancomycin class 3 obesity. However, the parametric model outperformed several other models, suggesting that institution-specific models may improve pharmacokinetics management.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140959592","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":"Developing Parametric and Nonparametric Models for Model-Informed Precision Dosing: A Quality Improvement Effort in Vancomycin for Patients With Obesity.","authors":"Maria-Stephanie A Hughes, Jasmine H. Hughes, Jeffrey Endicott, Meagan M. Langton, John W Ahern, Ron J. Keizer","doi":"10.1097/FTD.0000000000001214","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001214","url":null,"abstract":"BACKGROUND\u0000Both parametric and nonparametric methods have been proposed to support model-informed precision dosing (MIPD). However, which approach leads to better models remains uncertain. Using open-source software, these 2 statistical approaches for model development were compared using the pharmacokinetics of vancomycin in a challenging subpopulation of class 3 obesity.\u0000\u0000\u0000METHODS\u0000Patients on vancomycin at the University of Vermont Medical Center from November 1, 2021, to February 14, 2023, were entered into the MIPD software. The inclusion criteria were body mass index (BMI) of at least 40 kg/m2 and 1 or more vancomycin levels. A parametric model was created using nlmixr2/NONMEM, and a nonparametric model was created using metrics. Then, a priori and a posteriori predictions were evaluated using the normalized root mean squared error (nRMSE) for precision and the mean percentage error (MPE) for bias. The parametric model was evaluated in a simulated MIPD context using an external validation dataset.\u0000\u0000\u0000RESULTS\u0000In total, 83 patients were included in the model development, with a median age of 56.6 years (range: 24-89 years), and a median BMI of 46.3 kg/m2 (range: 40-70.3 kg/m2). Both parametric and nonparametric models were 2-compartmental, with creatinine clearance and fat-free mass as covariates to c clearance and volume parameters, respectively. The a priori MPE and nRMSE for the parametric versus nonparametric models were -6.3% versus 2.69% and 27.2% versus 30.7%, respectively. The a posteriori MPE and RMSE were 0.16% and 0.84%, and 13.8% and 13.1%. The parametric model matched or outperformed previously published models on an external validation dataset (n = 576 patients).\u0000\u0000\u0000CONCLUSIONS\u0000Minimal differences were found in the model structure and predictive error between the parametric and nonparametric approaches for modeling vancomycin class 3 obesity. However, the parametric model outperformed several other models, suggesting that institution-specific models may improve pharmacokinetics management.","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140993980","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":"CYP1A2 Polymorphism and Drug Co-administration Affect the Blood Levels and Adverse Effects of Pirfenidone.","authors":"Xuerong Yang, Jingxia Wei, Yong Yang, Yuanyuan He, Lu Guo, Xing He, Lijuan Zhang, Lu Chen","doi":"10.1097/FTD.0000000000001208","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001208","url":null,"abstract":"<p><strong>Background: </strong>Mutations in metabolic enzymes and co-administration of drugs may affect the blood concentration of pirfenidone effective in pulmonary fibrosis. To provide a basis for the precise clinical use of pirfenidone, the authors analyzed the correlation between steady-state pirfenidone trough concentration and adverse drug reactions (ADRs) and examined the impact of CYP1A2*1C (rs2069514) and *1F (rs762551) variants and co-administration on pirfenidone blood concentrations and ADRs.</p><p><strong>Methods: </strong>Forty-four patients were enrolled. The blood concentration of pirfenidone was determined using high-performance liquid chromatography. CYP1A2*1C and *1F genotypes were determined using direct SNP sequencing. Additional information related to drug associations was collected to screen factors affecting drug metabolism.</p><p><strong>Results: </strong>The highest predictive value of ADRs was observed when the steady-state trough concentration of pirfenidone was 3.18 mcg·mL-1 and the area under the receiver operating characteristic curve was 0.701 (P = 0.024). The pirfenidone concentration-to-dose ratio (C/D) in CYP1A2*1F homozygous AA mutants was lower than that in C carriers (CC+AC) (1.28 ± 0.85 vs. 2.03 ± 1.28 mcg·mL-1; P = 0.036). Adverse drug reaction (ADR) incidence in the homozygous AA mutant group (28.0%) was significantly lower than that in the C carriers (CC+AC) (63.2%; P = 0.020), and ADR incidence in the A carriers (AC+AA) was considerably lower than that in the CC group (85.7%; P = 0.039). The C/D value of the combined lansoprazole/rabeprazole group was lower than that of the noncombination group (P < 0.05).</p><p><strong>Conclusions: </strong>The ADR incidence was positively correlated with pirfenidone blood concentration. The CYP1A2 (rs762551) AA genotype is associated with lower pirfenidone concentrations and fewer ADRs. Lansoprazole/rabeprazole co-administration reduced pirfenidone concentrations. Randomized controlled trials should further explore personalized dosing of pirfenidone and combination therapies.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899545","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":"Daptomycin Exposure Prediction With a Limited Sampling Strategy.","authors":"Simona De Gregori, Elena Seminari, Mara Capone, Paola Giordani, Rsffaele Bruno, A. De Silvestri","doi":"10.1097/FTD.0000000000001211","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001211","url":null,"abstract":"BACKGROUND\u0000Daptomycin is a cyclic lipopeptide antibiotic used to treat serious infectious endocarditis caused by Staphylococcus aureus. The pharmacodynamic parameter correlating best with efficacy is the ratio of the estimated area under the concentration (AUC0-24)-time curve to the minimum inhibitory concentration. The aim of the study is to develop a limited sampling strategy to estimate AUC0-24 using a reduced number of samples.\u0000\u0000\u0000METHODS\u0000Sixty-eight daptomycin AUC0-24 values were calculated for 50 White patients who underwent treatment for at least 5 consecutive days. Plasma concentrations were detected using a validated high-performance liquid chromatography-tandem mass spectrometry analytical method, with daptomycin-d5 as an internal standard. Multiple regression was used to evaluate the ability of 2 concentration-time points to predict the AUC0-24 calculated from the entire pharmacokinetic profile. Prediction bias was calculated as the mean prediction error, whereas prediction precision was estimated as the mean absolute prediction error. The development and validation datasets comprised 40 and 10 randomly selected patients, respectively.\u0000\u0000\u0000RESULTS\u0000The AUC0-24 (mg*h/L) was best estimated using the daptomycin trough concentration and plasma concentrations detected 2 hours after dosing. We calculated a mean prediction error of 1.6 (95% confidence interval, -10.7 to 10.9) and a mean absolute prediction error of 11.8 (95% confidence interval, 5.3-18.3), with 73% of prediction errors within ±15%.\u0000\u0000\u0000CONCLUSIONS\u0000An equation was developed to estimate daptomycin exposure (AUC0-24), offering clinical applicability and utility in generating personalized dosing regimens, especially for individuals at high risk of treatment failure or delayed response.","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140657646","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 Pharmacokinetics of Lamotrigine and Its N2-Glucuronide Metabolite in Chinese Patients with Epilepsy.","authors":"Hua Yang, Dongjie Zhang, Shi-ge Wei, Zhigang Zhao, S. Mei","doi":"10.1097/FTD.0000000000001207","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001207","url":null,"abstract":"BACKGROUND\u0000Lamotrigine is a new antiepileptic drug with substantial interindividual variability in its pharmacokinetics and therapeutic responses. This study aimed to develop population pharmacokinetic (PPK) models of lamotrigine and its N2-glucuronide metabolites for model-informed individualized therapy.\u0000\u0000\u0000METHODS\u0000A total of 353 plasma concentrations from Chinese patients with epilepsy receiving oral lamotrigine were used to develop a population PPK model using a nonlinear mixed effects modeling method. One- and two-compartment models were applied to the nonmetabolite and metabolite model, respectively. Forward addition and backward elimination were used to establish the final model. Model validation was performed using standard goodness-of-fit, bootstrap, visual predictive checks, and normalized prediction distribution errors. Finally, simulations were performed to propose lamotrigine dosages in different situations to achieve trough concentrations within the reference interval (2.5-15 mg/L).\u0000\u0000\u0000RESULTS\u0000For both final population PPK models, coadministration with valproic acid (VPA) or enzyme inducer, and body weight significantly affected lamotrigine clearance. The final models for lamotrigine clearance were and for nonmetabolite and metabolite models, respectively. The precision of the PPK parameters was acceptable, and the models exhibited good predictability. Monte Carlo simulations revealed that the lamotrigine dosage administered to patients combined with an enzyme inducer must be tripled that administered with VPA to reach the target trough concentration.\u0000\u0000\u0000CONCLUSIONS\u0000Variability in the pharmacokinetics of lamotrigine is large. Coadministration of VPA or an enzyme inducer and body weight are the most important factors in lamotrigine clearance in Chinese patients with epilepsy. The developed population PPK models might support further optimization of lamotrigine dosing regimens.","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140665078","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":"Tacrolimus Monitoring in Liver Transplant Recipients, Posttransplant Cholestasis: A Comparative Between 2 Commercial Immunoassays and a Liquid Chromatography-Tandem Mass Spectrometry Method.","authors":"François Parant, Marie-Charlotte Delignette, Bruno Charpiat, Louis Lacaille, Fanny Lebosse, Guillaume Monneret, Kayvan Mohkam, Jean-Yves Mabrut, Frederic Aubrun, Laurent Heyer, Teresa Antonini","doi":"10.1097/ftd.0000000000001201","DOIUrl":"https://doi.org/10.1097/ftd.0000000000001201","url":null,"abstract":"Cholestasis commonly occurs after orthotopic liver transplantation. It can be extrahepatic because of mechanical obstruction or intrahepatic because of various causes. During cholestasis episodes, blood concentrations of tacrolimus (TAC) metabolites may increase, potentially affecting TAC concentrations measured by immunoassays. This study aimed to simultaneously evaluate the analytical performance of 2 TAC immunoassays, a quantitative microsphere system (QMS) immunoassay, and chemiluminescence microparticle immunoassay, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a reference method in liver transplant recipients.","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140634244","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":"Retrospective Analysis of Steady-State Sodium Valproate Plasma Concentrations in Chinese Patients With Bipolar Disorder: Impact of Demographic and Clinical Characteristics.","authors":"Qian Qiming, Zheng Ping, Li Huiqi, Xu Leyu, Li LIren, Lei Ming","doi":"10.1097/ftd.0000000000001199","DOIUrl":"https://doi.org/10.1097/ftd.0000000000001199","url":null,"abstract":"This study comprehensively examined the demographic and clinical characteristics of patients undergoing valproic acid therapy and explored their potential impact on plasma valproic acid concentrations. All enrolled patients were administered the extended-release formulation. An in-depth investigation of factors, including dose, age, sex, body mass index, co-administered medications, and laboratory test findings, was conducted to evaluate their potential influence on study outcomes.","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140634254","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 Lamotrigine Plasma Concentrations with Efficacy and Toxicity in Patients with Epilepsy: A Retrospective Study.","authors":"Ze-Ning Lee, Merel van Nuland, Tim Bognàr, Frans S S Leijten, Kim C M van der Elst","doi":"10.1097/ftd.0000000000001205","DOIUrl":"https://doi.org/10.1097/ftd.0000000000001205","url":null,"abstract":"There is limited evidence to support the currently suggested lamotrigine (LTG) therapeutic reference range of 2.5-15 mg/L for the treatment of seizures. The objective of this study was to evaluate the association of LTG plasma concentrations with the efficacy and toxicity of the treatment in patients with epilepsy.","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140634120","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":"Best Practice for Therapeutic Drug Monitoring of Infliximab: Position Statement from the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.","authors":"Dahham Alsoud, Dirk Jan A R Moes, Zhigang Wang, Rani Soenen, Zohra Layegh, Murray Barclay, Tomoyuki Mizuno, Iris K Minichmayr, Ron J Keizer, Sebastian G Wicha, Gertjan Wolbink, Jo Lambert, Séverine Vermeire, Annick de Vries, Konstantinos Papamichael, Núria Padullés-Zamora, Erwin Dreesen","doi":"10.1097/ftd.0000000000001204","DOIUrl":"https://doi.org/10.1097/ftd.0000000000001204","url":null,"abstract":"Infliximab, an anti-tumor necrosis factor monoclonal antibody, has revolutionized the pharmacological management of immune-mediated inflammatory diseases (IMIDs). This position statement critically reviews and examines existing data on therapeutic drug monitoring (TDM) of infliximab in patients with IMIDs. It provides a practical guide on implementing TDM in current clinical practices and outlines priority areas for future research.","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140634863","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}