Journal of Clinical Pharmacology最新文献_第3页

A Phenome-Wide Association Study of Marijuana Use and Circulating Biomarkers in the United States: National Health and Nutrition Examination Survey 2009-2018. 美国大麻使用和循环生物标志物的全现象关联研究：2009-2018年国家健康和营养检查调查。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-04-01 DOI: 10.1002/jcph.70022

Cancan Zhang, Elizabeth Mostofsky, Hui Zhang, Bo Zhang, Julia Lindenberg, Maelys J Amat, Kenneth J Mukamal

{"title":"A Phenome-Wide Association Study of Marijuana Use and Circulating Biomarkers in the United States: National Health and Nutrition Examination Survey 2009-2018.","authors":"Cancan Zhang, Elizabeth Mostofsky, Hui Zhang, Bo Zhang, Julia Lindenberg, Maelys J Amat, Kenneth J Mukamal","doi":"10.1002/jcph.70022","DOIUrl":"https://doi.org/10.1002/jcph.70022","url":null,"abstract":"This study aimed to assess the associations between recent cannabis use and 49 biochemical biomarkers in a representative sample of American adults, using data from the 2009-2018 National Health and Nutrition Examination Survey. A phenotype-wide association study (PheWAS) was conducted to uncover new biomarkers linked to cannabis use. The analysis included 19,926 adults aged 18-59, with a mean age of 38.93 years (50.8% women), and 36.7% reporting recent cannabis use. Metabolic associations included higher high-density lipoprotein (HDL) cholesterol (3.51 mg/dL, 95% CI [2.50, 4.62]) and lower glycohemoglobin (-0.09%, 95% CI [-0.15, -0.04]) and glucose (-2.39 mg/dL, 95% CI [-4.07, -0.70]). Hematological findings included higher hemoglobin (0.09 g/dL, 95% CI [0.02, 0.16]), mean erythrocyte volume (1.46 fL, 95% CI [1.12, 1.80]), mean erythrocyte hemoglobin (0.46 pg, 95% CI [0.32, 0.60]), erythrocyte volume fraction (0.31%, 95% CI [0.11%, 0.50%]), and lower erythrocyte counts (-0.04 million cells/µL, 95% CI [-0.07, -0.02]). Serum chemistry associations included higher bicarbonate (0.20 mmol/L, 95% CI [0.06, 0.35]) and lower chloride (-0.47 mmol/L, 95% CI [-0.69, -0.24]). Associations were also observed with 25 hydroxyvitamin-3 (OHD3) (2.38 nmol/L, 95% CI [0.55, 4.22]) and epi-25OHD3 (0.40 nmol/L, 95% CI [0.15, 0.65]), and an inverse association with globulin (-0.03 g/dL, 95% CI [-0.06, -0.01]). Sensitivity analyses confirmed the robustness of these associations. Recent marijuana use is associated with diverse and complex phenotypes, several of which have not been previously evaluated. Further validation studies are warranted, this approach offers an opportunity to understand a comprehensive range of potential effects of marijuana use.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755422","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

In Vitro and Clinical Evaluations of UGT1A1-, P-gp-, OATP1B1-, and BCRP-Mediated Drug-Drug Interactions of Belumosudil, a Potent ROCK2 Inhibitor. 有效的ROCK2抑制剂Belumosudil的UGT1A1-、P-gp-、OATP1B1-和bcrp介导的药物-药物相互作用的体外和临床评价

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-03-27 DOI: 10.1002/jcph.70018

Olivier Schueller, Lauren Lohmer, Felix Beck, Jeegar Patel, Jasminder Sahi

{"title":"In Vitro and Clinical Evaluations of UGT1A1-, P-gp-, OATP1B1-, and BCRP-Mediated Drug-Drug Interactions of Belumosudil, a Potent ROCK2 Inhibitor.","authors":"Olivier Schueller, Lauren Lohmer, Felix Beck, Jeegar Patel, Jasminder Sahi","doi":"10.1002/jcph.70018","DOIUrl":"https://doi.org/10.1002/jcph.70018","url":null,"abstract":"Belumosudil is an oral selective rho-associated coiled-coil containing protein kinase 2 inhibitor, approved as a treatment for chronic graft-versus-host disease. Prior clinical studies demonstrated that coadministration with strong CYP3A4 inducers or proton pump inhibitors requires dose modification of belumosudil. In vitro assessments suggested that belumosudil may inhibit uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), P-glycoprotein (P-gp), organic anion transporting polypeptide 1B1 (OATP1B1), and breast cancer resistance protein (BCRP), resulting in drug-drug interactions (DDIs). This three-part clinical DDI study (NCT05806567) was conducted to assess the effect of multiple doses of belumosudil (200 mg daily) on the single-dose pharmacokinetics of raltegravir (UGT1A1-sensitive substrate), dabigatran etexilate (P-gp-sensitive substrate), and rosuvastatin calcium (OATP1B1/BCRP-sensitive substrate). Although there was no marked change in raltegravir exposure after coadministration with belumosudil, exposure to the glucuronide metabolite was decreased by 39.6% (area under the curve from time 0 to the time of last measurable concentration [AUC0-last]) and 42.4% (maximum observed concentration [Cmax]), suggesting that belumosudil is an in vivo inhibitor of UGT1A1. There was an approximate 2-fold increase in Cmax, AUC0-last, and AUC from time 0 extrapolated to infinity (AUC0-inf) for dabigatran etexilate, suggesting a potential and clinically relevant DDI for belumosudil and sensitive P-gp substrates. Cmax and AUC0-last for rosuvastatin calcium increased by 3.6-fold and 4.6-fold, respectively, suggesting a clinically relevant interaction with drugs that are substrates of OATP1B1 or BCRP. There was no impact of coadministration with raltegravir, dabigatran etexilate, or rosuvastatin calcium on belumosudil pharmacokinetics, and belumosudil was well tolerated.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721438","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

Once- Versus Twice-Daily Tacrolimus Therapy: Does Improved Adherence Lead to Better Efficacy?-A Pharmacokinetic Perspective. 他克莫司每日一次与每日两次治疗：依从性的提高是否会带来更好的疗效？-药代动力学观点。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-03-27 DOI: 10.1002/jcph.70021

Zi-Yan Dai, Lu Han, Juan Wang, Xiao-Qin Liu, Rui Chen, Zheng Jiao

{"title":"Once- Versus Twice-Daily Tacrolimus Therapy: Does Improved Adherence Lead to Better Efficacy?-A Pharmacokinetic Perspective.","authors":"Zi-Yan Dai, Lu Han, Juan Wang, Xiao-Qin Liu, Rui Chen, Zheng Jiao","doi":"10.1002/jcph.70021","DOIUrl":"https://doi.org/10.1002/jcph.70021","url":null,"abstract":"Tacrolimus, a critical immunosuppressant in organ transplantation, is available in immediate-release (IR-T) and extended-release (ER-T) formulations. While ER-T improves patient adherence, clinical studies have not demonstrated superior outcomes compared to IR-T. However, the underlying reasons for this discrepancy remain unclear. This study aimed to evaluate tacrolimus exposure under non-adherent dosing behaviors with IR-T and ER-T and to provide insights for selecting the optimal tacrolimus formulation. Monte Carlo simulations were conducted to assess the proportion of target attainment (%PTA) and deviation time (DT) from the therapeutic range in scenarios involving delayed or missed doses, based on published population pharmacokinetic models. The influence of renal function, the post-transplantation period, and hematocrit levels on %PTA and DT were also analyzed. Our findings revealed that patients on ER-T exhibited lower %PTA and longer DT than those on IR-T when doses were delayed or missed, reflecting poorer \"forgiveness.\" This observation elucidates the lack of clinical superiority observed for ER-T in previous studies. Furthermore, fast metabolizers experienced worse forgiveness with ER-T, exacerbating the challenge of maintaining therapeutic levels. Additionally, a web-based dashboard was developed to calculate the %PTA and DT for individual patients and to provide formulation recommendations tailored to their dosing behaviors and clinical characteristics. In conclusion, adherence and forgiveness play a crucial role in the success of pharmacotherapy. This study highlights the significance of pharmacokinetic modeling and simulation in providing evidence-based recommendations for selecting the optimal tacrolimus formulation.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721740","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

Efanesoctocog Alfa Population Pharmacokinetics and Repeated Time-To-Event Analysis of Bleeds in Adults, Adolescents, and Children with Severe Hemophilia A. 成人、青少年和儿童A型严重血友病患者的血药代动力学和重复事件时间分析

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-03-23 DOI: 10.1002/jcph.70008

Nancy Wong, Pratik Bhagunde, Joakim Nyberg, Suresh Katragadda, Marek Demissie, Annemieke Willemze, Craig Benson, Sreeraj Macha

{"title":"Efanesoctocog Alfa Population Pharmacokinetics and Repeated Time-To-Event Analysis of Bleeds in Adults, Adolescents, and Children with Severe Hemophilia A.","authors":"Nancy Wong, Pratik Bhagunde, Joakim Nyberg, Suresh Katragadda, Marek Demissie, Annemieke Willemze, Craig Benson, Sreeraj Macha","doi":"10.1002/jcph.70008","DOIUrl":"https://doi.org/10.1002/jcph.70008","url":null,"abstract":"Efanesoctocog alfa is a first-in-class high-sustained factor VIII (HSF) replacement therapy for treatment of hemophilia A. This article presents population pharmacokinetics (PopPK) of efanesoctocog alfa and repeated time-to-event (RTTE) analysis of bleeding episodes in adults/adolescents (≥12 years of age) and children (<12 years). The final PopPK dataset contained pooled data from 277 patients (4405 post-dose factor VIII [FVIII] activity records) from two Phase 1/2a studies (NCT03205163; EudraCT 2018-001535-51), and three Phase 3 studies, XTEND-1 (NCT04161495), XTEND-Kids (NCT04759131), and XTEND-ed (NCT04644575). The PopPK model developed was a linear one-compartment model including body weight effect on clearance and volume of central compartment; Asian race was identified as a statistically significant covariate on clearance. The final PopPK model adequately described the FVIII activity-time profiles in adults, adolescents, and children with once-weekly (QW) efanesoctocog alfa 50 IU/kg, consistent with experience in XTEND-1 and XTEND-Kids. Bleeding episodes in participants in XTEND-1 and XTEND-Kids were characterized by an RTTE model with a Weibull base hazard and effect of FVIII activity modeled by a power effect. The RTTE model showed the probability of being bleed-free in 1 year with efanesoctocog alfa 50 IU/kg QW regimen was >70% across all age groups, consistent with the observed clinical outcomes in the Phase 3 trials of highly effective protection from bleeding episodes in patients with severe hemophilia A, which validates the model's prediction of the long-term bleed hazard.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694243","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

Population Pharmacokinetics and Exposure-Response Analyses of Sarilumab in Patients with Polymyalgia Rheumatica. Sarilumab在风湿性多肌痛患者中的人群药代动力学和暴露-反应分析。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-03-19 DOI: 10.1002/jcph.70019

Christine Xu, William S Denney, Ying Liu, Jennifer Sloane, Remco Diab, Hisham Abdallah, Sreeraj Macha, Bhaskar Dasgupta

{"title":"Population Pharmacokinetics and Exposure-Response Analyses of Sarilumab in Patients with Polymyalgia Rheumatica.","authors":"Christine Xu, William S Denney, Ying Liu, Jennifer Sloane, Remco Diab, Hisham Abdallah, Sreeraj Macha, Bhaskar Dasgupta","doi":"10.1002/jcph.70019","DOIUrl":"https://doi.org/10.1002/jcph.70019","url":null,"abstract":"Sarilumab (interleukin-6 receptor inhibitor) is approved in the United States and Europe for polymyalgia rheumatica (PMR). This study characterized sarilumab pharmacokinetics (PK) and assessed the influence of intrinsic and extrinsic factors on PK in patients with PMR and giant cell arteritis (GCA). Exposure-responses analyses were conducted to evaluate the PK-pharmacodynamic (PD) relationships of sarilumab with key efficacy and safety endpoints in patients with PMR (NCT03600818). Population (Pop) PK analysis was conducted using pooled PK data from two phase III studies including 58 patients with PMR and 40 with GCA (NCT03600805). This Pop PK model was developed by re-estimating parameters from a previous rheumatoid arthritis (RA) model. The main source of intrinsic PK variability in patients with PMR was body weight, with decreasing weight causing increased sarilumab exposure. The population mean apparent clearance for patients with PMR was lower than for patients with RA due to higher albumin, lower creatinine clearance, and lower C-reactive protein (CRP) in PMR than in RA. Individual exposures at steady state overlapped among patients with PMR, GCA, and RA. PK-PD relationships showed that greater sarilumab Ctrough in patients with PMR were associated with increasing total sIL-6Rα and decreasing CRP. There was a slight increase in patients achieving sustained remission at Week 52 and a decrease in absolute neutrophil count with increasing sarilumab Ctrough plateauing at 20-25 mg/L. The PD effect of sarilumab plateaued at Ctrough of 20-25 mg/L for target saturation, efficacy, and safety endpoints, supporting a dosage of 200 mg every 2 weeks for PMR.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659372","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

Cherishing Professional Success and Personal Fulfillment: Resilience as a Pivotal Leadership Competency for Clinical Pharmacologists and Beyond. 珍惜职业成功和个人实现：弹性作为临床药理学家和其他领域的关键领导能力。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-03-19 DOI: 10.1002/jcph.70017

Karthik Venkatakrishnan, Jing 'Daisy' Zhu, Federica Ferrari, Krista Levy, Beth Kennedy

{"title":"Cherishing Professional Success and Personal Fulfillment: Resilience as a Pivotal Leadership Competency for Clinical Pharmacologists and Beyond.","authors":"Karthik Venkatakrishnan, Jing 'Daisy' Zhu, Federica Ferrari, Krista Levy, Beth Kennedy","doi":"10.1002/jcph.70017","DOIUrl":"https://doi.org/10.1002/jcph.70017","url":null,"abstract":"Resilience is a critical leadership competency directly linked to engagement, sustainable innovation, and productivity. This Commentary presents resilience concepts using the Benatti Resiliency Model®, which comprises five inter-related dimensions: Well-being, Self-awareness, Brand, Connection, and Innovation. Trust is discussed as a critical leadership competency, with three levels: self-trust, trust in relationships at the team level, and community trust. The concept of Ikigai, representing the intersection of what one loves, what one is good at, what the world needs, and what one can be paid for, is discussed as a framework for self-awareness, brand development, development planning, and mentoring. Time and energy management using the Eisenhower matrix is highlighted as a strategy to build resilience, manage stress, enhance productivity, and prevent burnout. Taken together, the strategies discussed in this commentary are intended to unlock the transformative potential of resilience for sustainable innovation and impact within and beyond the dynamic and interdisciplinary field of clinical pharmacology, ultimately enabling professional success and personal fulfillment.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659342","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

Optimal Design of Drug-Drug Interaction Studies for the GLP-1 Receptor Agonist Drug Class for Weight Management: Closing a Potential Data Gap. 体重管理GLP-1受体激动剂药物类药物-药物相互作用研究的优化设计：关闭潜在的数据缺口。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-03-18 DOI: 10.1002/jcph.70020

Elijah Weber, Ashit Trivedi, April M Barbour

引用次数: 0

Dose Ranging in Pediatric Drug Development Trials Submitted to the US FDA 2012-2020. 2012-2020年向美国FDA提交的儿科药物开发试验的剂量范围。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-03-11 DOI: 10.1002/jcph.70016

Carlton K K Lee, Eugenia Kwon, Francis G Green, Connor M I Kelley, Jennifer Pham, Gelareh Abulwerdi, Sherbet Samuels, Dionna J Green, Gilbert J Burckart

{"title":"Dose Ranging in Pediatric Drug Development Trials Submitted to the US FDA 2012-2020.","authors":"Carlton K K Lee, Eugenia Kwon, Francis G Green, Connor M I Kelley, Jennifer Pham, Gelareh Abulwerdi, Sherbet Samuels, Dionna J Green, Gilbert J Burckart","doi":"10.1002/jcph.70016","DOIUrl":"https://doi.org/10.1002/jcph.70016","url":null,"abstract":"Dose selection is a critical process within pediatric drug development and dose-ranging studies are integral to establish a reasonable dose. The objective of this analysis was to examine the dose-ranging trials utilized in pediatric drug development and to determine (1) the dose-ranging strategies that were used in all available pediatric dose-ranging studies, (2) the success of achieving pediatric labeling in those submissions to the US Food and Drug Administration, and (3) ethical aspects of providing a prospect of direct benefit to pediatric patients in dose-ranging studies. Of the 275 programs that previously surveyed pediatric drug development programs from 2012 to 2020, it was determined that dose-ranging studies were used for 97 (35.3%) programs. The three categorizations of these 97 programs included the parallel dose design (n = 66; 68%), the dose-escalation design (n = 18; 18.6%), and the crossover design (n = 13; 13.4%). In the 66 that used a parallel design, 41 of these products were approved for use in pediatric patients. In 13 out of the 41 drugs (31.7%) approved for pediatric use using parallel dose ranging, the lowest parallel dose (patient on the dose for the entire study) was lower than the approved dose. Dose ranging remains an important strategy for optimizing dosing, but ethical considerations and the need to optimize benefit for individual patients should drive decisions about dosing approaches in pediatric patients. The inclusion of adaptive designs is one possible approach to optimizing dose-ranging studies for pediatric patients.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598113","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

Pharmacokinetics and Safety of Fenofibrate in Participants with Mild Hepatic Impairment or with Advanced Fibrosis due to Metabolic-Associated Fatty Liver Disease. 非诺贝特在代谢性脂肪肝引起的轻度肝功能损害或晚期纤维化患者中的药代动力学和安全性

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-03-07 DOI: 10.1002/jcph.70005

Islam R Younis, Elijah J Weber, Cara Nelson, Ann R Qin, Timothy R Watkins, Ahmed A Othman

{"title":"Pharmacokinetics and Safety of Fenofibrate in Participants with Mild Hepatic Impairment or with Advanced Fibrosis due to Metabolic-Associated Fatty Liver Disease.","authors":"Islam R Younis, Elijah J Weber, Cara Nelson, Ann R Qin, Timothy R Watkins, Ahmed A Othman","doi":"10.1002/jcph.70005","DOIUrl":"https://doi.org/10.1002/jcph.70005","url":null,"abstract":"Fenofibrate is contraindicated in patients with advanced hepatic fibrosis due to limited clinical data. We evaluated the pharmacokinetics and safety of fenofibrate in participants with mild hepatic impairment (phase 1 study) or advanced fibrosis due to metabolic-associated fatty liver disease (MAFLD; phase 2a study). In the phase 1 study, participants with mild hepatic impairment and healthy matched controls (each n = 10) received a single, oral dose of fenofibrate 48 mg. In the phase 2a study, participants with hypertriglyceridemia and advanced fibrosis due to MAFLD were randomly assigned (1:1) fenofibrate 48 mg (n = 15) or fenofibrate 145 mg (n = 16) combined with firsocostat 20 mg, taken orally once daily for 24 weeks. Pharmacokinetics and safety were assessed in both studies. In the phase 1 study, the AUCinf of fenofibric acid was 25% higher in participants with mild hepatic impairment than in healthy matched participants. In the phase 2a study, the AUCss,0-24 of fenofibric acid (fenofibrate 48 mg dose) in participants with F3 fibrosis and F4 cirrhosis was approximately 60% and 80%, respectively, higher than the AUCinf in healthy participants in the phase 1 study, and was 20% higher in participants with F4 cirrhosis than in participants with F3 fibrosis. In both studies, most adverse events and laboratory abnormalities were grade 1-2. In the phase 2a study, three participants had grade 3 hypertriglyceridemia. Fenofibrate was well tolerated, and modest differences were observed in fenofibric acid exposure in participants with mild hepatic impairment or advanced fibrosis due to MAFLD.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574419","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

Contemporary Use of Oral Inotropes in the Outpatient Treatment of Heart Failure: Analysis of a Japanese Nationwide Database. 当代口服肌力药物在心衰门诊治疗中的应用：对日本全国数据库的分析。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-03-03 DOI: 10.1002/jcph.70015

Michikazu Nakai, Yoshitaka Iwanaga, Koshiro Kanaoka, Yoko Sumita, Yuichi Nishioka, Tomoya Myojin, Katsuki Okada, Tatsuya Noda, Tomoaki Imamura, Yoshihiro Miyamoto

{"title":"Contemporary Use of Oral Inotropes in the Outpatient Treatment of Heart Failure: Analysis of a Japanese Nationwide Database.","authors":"Michikazu Nakai, Yoshitaka Iwanaga, Koshiro Kanaoka, Yoko Sumita, Yuichi Nishioka, Tomoya Myojin, Katsuki Okada, Tatsuya Noda, Tomoaki Imamura, Yoshihiro Miyamoto","doi":"10.1002/jcph.70015","DOIUrl":"https://doi.org/10.1002/jcph.70015","url":null,"abstract":"Clinical evidence of oral inotrope use for advanced heart failure (HF) is limited. This study investigated the contemporary use and association of oral inotropes with prognosis in the outpatient treatment of advanced HF using a nationwide administrative claims database in Japan. Patients hospitalized with acute HF between 2014 and 2021 were identified from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. Associations of the drug use after discharge with the 2-year prognosis were examined in a propensity-matching cohort, and hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Of the 428,650 patients discharged with HF in 4433 hospitals, 14,374 (3.4%) had taken oral inotropes, most of whom (95.0%) took pimobendan. Patients taking oral inotropes were younger and more likely to receive HF drugs. Cardiomyopathy as the etiology and the use of intravenous inotropes during hospitalization were more frequently observed. In the 2-year prognosis, oral inotrope use was associated with higher all-cause mortality and HF rehospitalization rates (HR [95% CI]: 1.59 [1.51, 1.66] and 1.54 [1.48, 1.61], respectively). Concomitant use of pimobendan and β-blockers was associated with lower mortality and HF rehospitalization (0.81 [0.74, 0.88] and 0.85 [0.79, 0.92], respectively) compared with pimobendan without β-blockers. Although no association was found between oral inotrope use and favorable prognosis, concomitant use of β-blockers may be a better strategy for oral inotrope use in advanced HF.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544166","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