Therapeutic Drug Monitoring最新文献

筛选
英文 中文
Population Pharmacokinetic Modeling of Pyrazinamide Among Chinese Patients With Drug-Sensitive or Multidrug-Resistant Tuberculosis. 吡嗪酰胺在中国药物敏感或耐多药肺结核患者中的人群药代动力学模型。
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2024-09-06 DOI: 10.1097/FTD.0000000000001255
Shuyan Chen, Weiqiao Rao, Liang Fu, Guohui Liu, Jiancong Zhang, Yunli Liao, Ning Lv, Guofang Deng, Shijin Yang, Liang Lin, Lujin Li, Jiuxin Qu, Siqi Liu, Jin Zou
{"title":"Population Pharmacokinetic Modeling of Pyrazinamide Among Chinese Patients With Drug-Sensitive or Multidrug-Resistant Tuberculosis.","authors":"Shuyan Chen, Weiqiao Rao, Liang Fu, Guohui Liu, Jiancong Zhang, Yunli Liao, Ning Lv, Guofang Deng, Shijin Yang, Liang Lin, Lujin Li, Jiuxin Qu, Siqi Liu, Jin Zou","doi":"10.1097/FTD.0000000000001255","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001255","url":null,"abstract":"<p><strong>Background: </strong>Pyrazinamide is used to treat drug-susceptible (DS) and multidrug-resistant (MDR) tuberculosis (TB). This study aimed to characterize the factors associated with the pharmacokinetic parameters of pyrazinamide and evaluate the disposition of the current regimen, which could provide suggestions for adequate dosing strategies for therapeutic targets.</p><p><strong>Methods: </strong>A population pharmacokinetic model of pyrazinamide was developed based on the data from 499 plasma concentrations from 222 Chinese patients diagnosed with DS or MDR TB. Pyrazinamide exposure was best described using a one-compartment model.</p><p><strong>Results: </strong>No significant differences were observed in the pharmacokinetic parameters between DS and MDR TB. The final covariate model showed that total body weight was the only significant covariate for apparent clearance, which increased by 0.45 L/h with a 10 kg increase in body weight. A simulation showed that for typical subjects weighing 40-80 kg, a fixed dosage of 1500 mg daily had an area under the concentration-time curve from 0 to 24 hours (AUC0-24) of 389.9-716.0 mg·h/L and peak serum concentrations of the drug (Cmax) of 32.2-44.8 mg/L.</p><p><strong>Conclusions: </strong>Fixed pyrazinamide doses of 1500, 1750, and 2000 mg are recommended for patients weighing 40-70, 70-80, and 80-90 kg, respectively, to achieve the exposure targets of AUC0-24 > 363 mg·h/L or Cmax > 35 mg/L to attain efficacy.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143380","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}
引用次数: 0
The Case of Dolutegravir Plus Darunavir Antiretroviral Regimens: Is It Always Useful to Double the Drug Doses? A Short Communication. 多罗替拉韦加达鲁那韦抗逆转录病毒疗法的案例:药物剂量加倍是否总是有用?简短交流。
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2024-09-05 DOI: 10.1097/FTD.0000000000001259
Dario Cattaneo, Anna Lisa Ridolfo, Andrea Giacomelli, Antonella Castagna, Alberto Dolci, Spinello Antinori, Cristina Gervasoni
{"title":"The Case of Dolutegravir Plus Darunavir Antiretroviral Regimens: Is It Always Useful to Double the Drug Doses? A Short Communication.","authors":"Dario Cattaneo, Anna Lisa Ridolfo, Andrea Giacomelli, Antonella Castagna, Alberto Dolci, Spinello Antinori, Cristina Gervasoni","doi":"10.1097/FTD.0000000000001259","DOIUrl":"https://doi.org/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":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-09-05","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}
引用次数: 0
Association of Plasma Cabozantinib Concentration With Treatment Response and Adverse Events in Japanese Patients With Advanced Renal Cell Carcinoma. 日本晚期肾细胞癌患者血浆中卡博替尼浓度与治疗反应和不良事件的关系
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2024-08-29 DOI: 10.1097/FTD.0000000000001254
Shinichi Maruyama, Hiroaki Kobayashi, Tatsuru Hiraga, Tadatsugu Anno, Tansei Sanjo, Masashi Arai, Masaru Ishida, Hiroshi Kanno, Masaru Kato
{"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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-29","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}
引用次数: 0
Dried Blood Spot Method Development and Clinical Validation for the Analysis of Elexacaftor, Elexacaftor-M23, Tezacaftor, Tezacaftor-M1, Ivacaftor, Ivacaftor Carboxylate, and Hydroxymethyl Ivacaftor Using LC-MS/MS. 利用 LC-MS/MS,开发分析 Elexacaftor、Elexacaftor-M23、Tezacaftor、Tezacaftor-M1、Ivacaftor、Ivacaftor Carboxylate 和 Hydroxymethyl Ivacaftor 的干血斑方法并进行临床验证。
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2024-08-27 DOI: 10.1097/FTD.0000000000001231
Steffie E M Vonk, Marloes van der Meer-Vos, Renate Kos, Anne H Neerincx, Suzanne W J Terheggen-Lagro, Josje Altenburg, Anke H Maitland-van der Zee, Ron A A Mathôt, E Marleen Kemper
{"title":"Dried Blood Spot Method Development and Clinical Validation for the Analysis of Elexacaftor, Elexacaftor-M23, Tezacaftor, Tezacaftor-M1, Ivacaftor, Ivacaftor Carboxylate, and Hydroxymethyl Ivacaftor Using LC-MS/MS.","authors":"Steffie E M Vonk, Marloes van der Meer-Vos, Renate Kos, Anne H Neerincx, Suzanne W J Terheggen-Lagro, Josje Altenburg, Anke H Maitland-van der Zee, Ron A A Mathôt, E Marleen Kemper","doi":"10.1097/FTD.0000000000001231","DOIUrl":"10.1097/FTD.0000000000001231","url":null,"abstract":"<p><strong>Background: </strong>The highly effective Cystic Fibrosis Transmembrane conductance Regulator (CFTR) modulator, elexacaftor-tezacaftor-ivacaftor, is now widely being used by people with cystic fibrosis. However, few independent studies have detailed the pharmacokinetics (PK) of CFTR modulators. Blood collection by venipuncture is the gold standard for PK measurements, but it is invasive. The aim of this study was to develop and clinically validate a quantification method for elexacaftor, tezacaftor, ivacaftor, and their main metabolites in dried blood spots (DBSs) using liquid chromatography with tandem mass spectrometry.</p><p><strong>Methods: </strong>Linearity, accuracy, precision, stability, hematocrit (Hct), spot-to-spot carryover, spot volume, and extraction efficiency were validated in DBS for all analytes. The clinical validation of elexacaftor-tezacaftor-ivacaftor in patients was performed by comparing 21 DBS samples with matched plasma samples.</p><p><strong>Results: </strong>The preset requirements for linearity, within-run and between-run accuracy, precision, Hct, spot volume, and extraction efficiency were met. Puncher carryover was observed and resolved by punching 3 blanks after each sample. The samples remained stable and showed no notable degradation across the tested temperatures and time intervals. Corrected DBS values with the Passing-Bablok regression equation showed good agreement in Bland-Altman plots, and acceptance values were within 20% of the mean for a minimum of 67% of the repeats, according to the EMA guidelines.</p><p><strong>Conclusions: </strong>A quantification method for the analysis of elexacaftor, tezacaftor, ivacaftor, and their main metabolites was developed and clinically validated in DBS. This method could be valuable in both clinical care and research to address unanswered PK questions regarding CFTR modulators.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141459470","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}
引用次数: 0
Unpredictable Cyclosporine Clearance in a Korean Patient with Aplastic Anemia With Adverse Effects: A Case Study. 一名韩国再生障碍性贫血患者无法预测的环孢素清除率及不良反应:病例研究。
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2024-08-20 DOI: 10.1097/FTD.0000000000001244
Renata Shihmanter, Edward B Miller, Ekaterina Shvartsman, Haim Shmuely
{"title":"Unpredictable Cyclosporine Clearance in a Korean Patient with Aplastic Anemia With Adverse Effects: A Case Study.","authors":"Renata Shihmanter, Edward B Miller, Ekaterina Shvartsman, Haim Shmuely","doi":"10.1097/FTD.0000000000001244","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001244","url":null,"abstract":"<p><strong>Abstract: </strong>A 29-year-old Korean woman with chronic aplastic anemia presented with seizures due to cyclosporine-induced posterior reversible encephalopathy syndrome, caused by unpredictable oral cyclosporine (CS) accumulation and prolonged elimination. This case demonstrates the need to monitor CS drug levels with careful dose adjustments.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081558","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}
引用次数: 0
A Refined Population Pharmacokinetic Model-Based Guideline for Individualized PEGasparaginase Dosing in Pediatric Acute Lymphoblastic Leukemia. 基于人群药代动力学模型的儿科急性淋巴细胞白血病患者PEG天冬酰胺酶个体化用药指南。
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2024-08-13 DOI: 10.1097/FTD.0000000000001252
Leiah J Brigitha, Karen Zaky, Rob Pieters, Inge M van der Sluis
{"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":"https://doi.org/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/m2 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":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-13","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}
引用次数: 0
Simultaneous Determination of Ripretinib and Its Desmethyl Metabolite in Human Plasma Using LC-MS/MS. 利用 LC-MS/MS 同时测定人体血浆中的瑞普替尼及其去甲基代谢物
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2024-08-06 DOI: 10.1097/FTD.0000000000001245
Zhou-Yi Qian, Ping Wang, Zi-Yi Wang, Yang Zhao, Tian-Tian Du, Hao Xu, Yong-Qing Wang, Lu-Ning Sun
{"title":"Simultaneous Determination of Ripretinib and Its Desmethyl Metabolite in Human Plasma Using LC-MS/MS.","authors":"Zhou-Yi Qian, Ping Wang, Zi-Yi Wang, Yang Zhao, Tian-Tian Du, Hao Xu, Yong-Qing Wang, Lu-Ning Sun","doi":"10.1097/FTD.0000000000001245","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001245","url":null,"abstract":"<p><strong>Background: </strong>Ripretinib, a recently developed tyrosine kinase inhibitor with switch-control abilities, can inhibit both primary and secondary activation of KIT(KIT proto-oncogene receptor tyrosine kinase) and platelet-derived growth factor receptor alpha (PDGFRA) mutants, which contribute to gastrointestinal stromal tumor progression.</p><p><strong>Methods: </strong>In this study, a high-performance liquid chromatography-tandem mass spectrometry method to measure the concentrations of ripretinib and its active desmethyl metabolite DP-5439 in human plasma was developed and validated. Plasma samples were extracted and recovered by precipitation with acetonitrile containing the internal standard and diluted with acetonitrile before analysis. Ripretinib and DP-5439 were separated using chromatography on a Waters ACQUITY UPLC HSS T3 column (2.1 mm × 50 mm, 1.8 μm) with gradient elution using 0.1% formic acid and 5 mM ammonium formate in water as mobile phase A and acetonitrile as mobile phase B. The mobile phase was set to a flow rate of 0.5 mL/min.</p><p><strong>Results: </strong>The calibration curves were linear across the following concentration range: 7.5 to 3000 ng/mL for ripretinib and 10 to 4000 ng/mL for DP-5439. The intraday and interday precisions were approximately 15% for all analytes in the quality control samples. The relative matrix effects in extracted plasma samples (90.3%-108.8% at different levels) were considered acceptable.</p><p><strong>Conclusions: </strong>This method will be a useful tool in oncology to facilitate the further clinical development of ripretinib.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902947","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}
引用次数: 0
Model-Informed Dosing Optimization of Tacrolimus for Concomitant Administration with Itraconazole to Japanese Lung Transplant Recipients. 根据模型优化日本肺移植受者他克莫司与伊曲康唑同服的剂量。
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2024-08-06 DOI: 10.1097/FTD.0000000000001249
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
{"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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-06","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}
引用次数: 0
Development and Validation of a Sensitive Liquid Chromatography-Tandem Mass Spectrometry Method for Therapeutic Drug Monitoring of Ceftolozane and Tazobactam in Human Plasma Microsamples. 开发并验证用于人体血浆微量样本中头孢妥仑和他唑巴坦治疗药物监测的灵敏液相色谱-串联质谱法
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2024-08-06 DOI: 10.1097/FTD.0000000000001236
Matteo Conti, Beatrice Giorgi, Milo Gatti, Pierluigi Viale, Federico Pea
{"title":"Development and Validation of a Sensitive Liquid Chromatography-Tandem Mass Spectrometry Method for Therapeutic Drug Monitoring of Ceftolozane and Tazobactam in Human Plasma Microsamples.","authors":"Matteo Conti, Beatrice Giorgi, Milo Gatti, Pierluigi Viale, Federico Pea","doi":"10.1097/FTD.0000000000001236","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001236","url":null,"abstract":"<p><strong>Background: </strong>Ceftolozane/tazobactam (C-T) is a novel beta-lactam/beta-lactamase inhibitor combination approved for the treatment of various infections caused by difficult-to-treat Pseudomonas aeruginosa. In critically ill patients, C-T may exhibit significant pharmacokinetic variability, both between individuals and within individuals, warranting therapeutic drug monitoring for clinical purposes. We aim to develop and validate a novel and sensitive analytical method for concurrently determining C and T in human plasma microsamples (3 μL).</p><p><strong>Methods: </strong>The method was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with positive electrospray ionization and multiple reaction monitoring (MRM) detection modes, employing specific mass transitions for both drugs. Sample preparation was simple, and the chromatographic run lasted only 4 minutes. Validation was conducted according to European Medicines Agency (EMA) guidelines, encompassing specificity, sensitivity, linearity, precision, accuracy, matrix effect, extraction recovery, limit of quantification, and drug stability. The validated method was applied to measure C and T in 32 plasma samples collected from critically ill patients with multidrug-resistant, gram-negative, bacterial infections.</p><p><strong>Results: </strong>The method ensured accurate (BIAS% 2.1-9.6 for C and -2.2 to 15.2 for T) and precise intraday CV% for C: 6.7-5.5; for T: 1.3-8.9; interday CV% for C 6.0-10.8; for T 4.1-10.2) measurements of C-T over a wide concentration range (0.2-200.0 mg/L for C and 0.1-100.0 mg/L for T). Overall, the recovery at quality control concentration levels was high for both C and T (mean values: 90-91 for C and 89-92 for T). Analyte stability was satisfactory in both human plasma and extracts under various storage conditions. The clinical applicability of the assay was confirmed by the reliably quantifying C and T in clinical plasma samples.</p><p><strong>Conclusions: </strong>The developed and validated LC-MS/MS method is sensitive and suitable for monitoring C and T in human plasma microsamples.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902945","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}
引用次数: 0
Prevalence of Psychoactive Substance Use During Pregnancy in Argentine Women: A Pilot Study Testing Maternal Hair. 阿根廷妇女在怀孕期间使用精神活性物质的流行率:一项测试母体毛发的试点研究。
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2024-08-01 Epub Date: 2024-05-07 DOI: 10.1097/FTD.0000000000001218
Melina Vieiros, Afrouz Mirahi, Marina Villarreal, Anna Ramos-Triguero, Iria Fernández-Rubal, Vicente Andreu-Fernández, Simona Pichini, Óscar García-Algar, Emilia Marchei
{"title":"Prevalence of Psychoactive Substance Use During Pregnancy in Argentine Women: A Pilot Study Testing Maternal Hair.","authors":"Melina Vieiros, Afrouz Mirahi, Marina Villarreal, Anna Ramos-Triguero, Iria Fernández-Rubal, Vicente Andreu-Fernández, Simona Pichini, Óscar García-Algar, Emilia Marchei","doi":"10.1097/FTD.0000000000001218","DOIUrl":"10.1097/FTD.0000000000001218","url":null,"abstract":"<p><strong>Background: </strong>The use of psychoactive substances (PSs) during pregnancy is a major public health concern because of their increasing prevalence worldwide. This study examined the understudied issue of gestational PS consumption in a cohort of Argentine delivering mothers.</p><p><strong>Methods: </strong>A cross-sectional pilot study involving 51 women receiving delivery care was conducted at the Santa Rosa Hospital in La Pampa, Argentina. Information on maternal sociodemographic characteristics, pregnancy history, and drug use was obtained through standardized interviews. Maternal hair samples were analyzed for alcohol, tobacco, licit, illicit, and prescription substance biomarkers using ultra-high-performance liquid chromatography high-resolution mass spectrometry and gas chromatography mass spectrometry.</p><p><strong>Results: </strong>During pregnancy, 49.0% of participants reported alcohol consumption, 25.5% reported tobacco use, and 23.5% reported cannabis use. Hair samples from 56.9% of the women were positive for illicit PSs, with the most frequent being cocaine (41.2%) and cannabis (15.7%). Among the women, 47.1% consumed alcohol during pregnancy. Of the 24 women with hair ethyl glucuronide ≥5 pg/mg, 33.3% drank until the end of gestation and 58.3% started a social drinking habit in the second half. The analysis also detected prescription substances (anticonvulsants, antidepressants, methadone, opioids, antihistamines, antiemetics, and analgesics), caffeine (70.6%), lidocaine, and levamisole, some of which were cocaine or opioid adulterants.</p><p><strong>Conclusions: </strong>This is the first study to objectively assess the consumption of licit and illicit PSs during pregnancy in Argentina. In contrast to most nearby countries, cocaine was the most detected illicit PS in this cohort of Argentine delivering women. This finding highlights the importance of regular monitoring of local trends in PS use during pregnancy.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899557","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}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信