Cts-Clinical and Translational Science最新文献

{"title":"Hemodynamic and Pharmacokinetic Interactions of TPN171 with Alcohol in Healthy Male Subjects","authors":"Jie Cheng,&nbsp;Hongjie Qian,&nbsp;Yu Wang,&nbsp;Liyu Liang,&nbsp;Wenjing Xu,&nbsp;Ye Liu,&nbsp;Qian Chen,&nbsp;Chen Yu,&nbsp;Huaqing Duan,&nbsp;Zhen Wang,&nbsp;Hang Wang,&nbsp;Jingying Jia","doi":"10.1111/cts.70165","DOIUrl":"https://doi.org/10.1111/cts.70165","url":null,"abstract":"<p>This study aimed to evaluate the effects of the concomitant administration of TPN171 and alcohol on hemodynamic and pharmacokinetic characteristics in healthy Chinese male subjects. Fifteen eligible subjects were randomly assigned to one of three sequences, each comprising three treatments: Treatment A (placebo +0.5 g/kg alcohol), Treatment B (TPN171 + 0.5 g/kg alcohol), and Treatment C (TPN171 + placebo). Enrolled subjects were administered with 10 mg TPN171 and/or 0.5 g/kg alcohol in fasting state in a randomized crossover design. Blood pressure, pulse rate (PR), blood samples, and breath alcohol test were measured at designated time points for hemodynamic and pharmacokinetic analyses. Compared with 10 mg TPN171 alone, administration of 10 mg TPN171 + 0.5 g/kg alcohol significantly lowered the area under the effect–time curve from 0 to 4 h (AUEC_0-4h) of systolic blood pressure (95% confidence interval [CI]: −29.75 to −0.83, <i>p</i> = 0.039) and significantly increased AUEC_0–4h of PR (95% CI: 7.47–28.92, <i>p</i> = 0.003). Compared with 0.5 g/kg alcohol alone, administration of 10 mg TPN171 + 0.5 g/kg alcohol contributed to significantly higher maximal increase of PR (95% CI: 2.78–9.44, <i>p</i> = 0.002) and AUEC_0-4h of PR (95% CI: 1.08–24.52, <i>p</i> = 0.035). Alcohol had no influence on the pharmacokinetics of TPN171, and vice versa. Though the concomitant administration of TPN171 and alcohol induced a more pronounced increase in PR, this did not result in clinical symptoms or heart rate increase-related adverse events, indicating that the combined use was generally safe and well-tolerated.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70165","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Participant-Centered Engagement for Sustained Adherence to Smartwatches: A 12-Month Prospective Decentralized Digital Health Study","authors":"Angelina R. Wilton,&nbsp;Christina T. Saliba,&nbsp;Jean Marrero-Polanco,&nbsp;Katharine Sheffield,&nbsp;Quantia Wilkes,&nbsp;Miriam Anacker,&nbsp;Paul E. Croarkin,&nbsp;Mohit Chauhan,&nbsp;Liselotte N. Dyrbye,&nbsp;Sherry Chesak,&nbsp;William V. Bobo,&nbsp;Arjun P. Athreya","doi":"10.1111/cts.70155","DOIUrl":"https://doi.org/10.1111/cts.70155","url":null,"abstract":"<p>Adherence in digital health studies with extended observation periods (≥ 12 months) is limited, and participant retention considerably reduces with time. The US Food and Drug Administration has issued guidelines for improving participant engagement, adherence, and diversity in digital health studies combined with decentralized procedures. A decentralized digital health study on well-being was designed with protocolized procedures to study the feasibility of participant engagement and technology support to facilitate adherence (wearing the smartwatch ≥ 70% of time) sustained over a 12-month period. At the end of the study, participants were asked about their ease of participation and free-response questions about how wearing the smartwatches impacted their physical wellness. An inductive thematic analysis (ITA) was performed to assess themes of those responses and association with adherence. A total of 298 participants were recruited between 2022 and 2023 (<i>n</i> = 129 in Cohort A in October 22, <i>n</i> = 169 in Cohort B in April 23), with 23% non-white participants accrued. Among the 298 participants accrued, 273 (92% of accrued participants) completed the 12-month study with an average overall adherence of 77.4% (SD = 32.64) wear-time across 12 months. Median adherence of participants whose responses exemplified an ITA theme encompassing perceived behavior changes in sleep and physical activity was higher than those who did not have a response exemplifying that theme. Conversely, those expressing perceived discomfort or intrusiveness of the smartwatch had a statistically lower adherence. These results highlight the crucial roles of technology support and robust engagement efforts to enable sustained adherence over extended follow-up periods in decentralized digital health studies.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70155","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of major adverse cardiovascular events in CYP2C19 LoF genotype guided clopidogrel against alternative antiplatelets for CAD patients undergoing PCI: Meta-analysis","authors":"Mohitosh Biswas,&nbsp;Murshadul Alam Murad,&nbsp;Maliheh Ershadian,&nbsp;Most Sumaiya Khatun Kali,&nbsp;Chonlaphat Sukasem","doi":"10.1111/cts.70080","DOIUrl":"https://doi.org/10.1111/cts.70080","url":null,"abstract":"<p>Selection of rational antagonists of P2Y₁₂ receptor for CAD patients who inherit <i>CYP2C19</i> LoF alleles remains still conflicting. This study compared the clinical outcomes in CAD patients inheriting <i>CYP2C19</i> LoF alleles undergoing PCI and treated with clopidogrel against alternative antagonists of P2Y₁₂ receptor. A thorough literature search was performed across multiple scientific databases following the PRISMA guidelines and PICO model. Setting the statistical significance at <i>p</i> &lt; 0.05 and RevMan software was used to calculate the risk ratios (RRs). Estimation of the pooled analysis revealed a significant 62% increased risk of major adverse cardiovascular events (MACE) in CAD patients inheriting <i>CYP2C19</i> LoF alleles and treated with clopidogrel against those treated with alternative P2Y₁₂ receptor antagonists such as prasugrel or ticagrelor (RR 1.62; 95% CI 1.42–1.86; <i>p</i> &lt; 0.00001). In addition, Asian CAD patients were found at a significantly higher risk of MACE (RR 1.93; 95% CI: 1.49–2.49; <i>p</i> &lt; 0.00001) juxtaposed to CAD patients of other ethnicities (RR 1.51; 95% CI: 1.29–1.78; <i>p</i> &lt; 0.00001). Conversely, between these two treatment groups, taking clopidogrel against prasugrel/ticagrelor, who possess <i>CYP2C19</i> LoF alleles, no significant differences in bleeding events were observed (RR 0.94; 95% CI 0.79–1.11; <i>p</i> = 0.47). CAD patients undergoing PCI who inherited <i>CYP2C19</i> LoF alleles and treated with clopidogrel were associated with significantly higher risk of MACE against those treated with alternative antagonists of P2Y₁₂ receptor, that is, prasugrel or ticagrelor.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global Trends in the Value of Author Order Across Medical Publications: A Cross-Sectional Bibliometric Study","authors":"Hidenori Hashimoto,&nbsp;Miwa Sekine,&nbsp;Yuji Nishizaki,&nbsp;David Aune,&nbsp;Atsushi Mizuno,&nbsp;Yasuhiro Homma,&nbsp;Yasuhiko Kiyama,&nbsp;Shoji Sanada,&nbsp;Shigeki Aoki","doi":"10.1111/cts.70157","DOIUrl":"https://doi.org/10.1111/cts.70157","url":null,"abstract":"<p>This study aimed to analyse the value of author order across countries, within the ‘Medicine General Internal’ and ‘Surgery’ fields, to enhance transparency and fairness in academic evaluations, particularly in international collaborative research. A cross-sectional bibliometric study was conducted using data from 2,845,748 papers published in 2022 across over 18,000 journals listed on Web of Science. The study focused on 124,736 papers from the ‘Medicine General Internal’ and ‘Surgery’ fields published in the top 19 countries. The analysis examined the position of the corresponding author relative to other co-authors by country and specialty. Hierarchical clustering was applied to identify patterns and group countries based on author order. Three distinct clusters were identified with regard to the corresponding author's position. In Cluster A (South Korea, China and Taiwan), the corresponding author was often the last author. In Cluster B (India, Japan, Italy, Türkiye and Spain), the corresponding author was frequently the second author. Cluster C (the United States, England and Germany) included countries where the corresponding author was typically the first author. The findings underscore the need for clear, internationally accepted author order standards. Establishing such standards is crucial for promoting fairness, transparency and efficiency in international collaborative research and for ensuring equitable scientific communication.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70157","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics of SARS-CoV-2 RNA Polymerase Inhibitor Remdesivir in Participants With Moderate and Severe Hepatic Impairment","authors":"Sean Regan,&nbsp;Rita Humeniuk,&nbsp;Luzelena Caro,&nbsp;Mazin Abdelghany,&nbsp;Santosh Davies,&nbsp;Amarylliz Baysa,&nbsp;Gong Shen,&nbsp;Robert H. Hyland,&nbsp;Aryun Kim","doi":"10.1111/cts.70159","DOIUrl":"https://doi.org/10.1111/cts.70159","url":null,"abstract":"<p>Remdesivir is an RNA polymerase inhibitor of severe acute respiratory syndrome coronavirus 2 administered intravenously (IV) that is approved for the treatment of coronavirus disease 2019 in hospitalized and nonhospitalized patients. The clinical dosing regimen is a single loading dose of 200 mg on Day 1 followed by once-daily maintenance doses of 100 mg from Day 2, for a total duration of up to 10 days. The prodrug, remdesivir, undergoes metabolic activation inside the cell to form the intracellular active metabolite (GS-443902) along with two plasma metabolites (GS-704277 and GS-441524). The pharmacokinetics and safety of a single IV 100-mg dose of remdesivir were evaluated in a Phase 1, open-label, multicenter study in participants with moderate (<i>n</i> = 10) or severe (<i>n</i> = 6) hepatic impairment (Child–Pugh–Turcotte Class B or C, respectively) and participants with normal liver function (<i>n</i> = 16). Compared with the normal hepatic function group, plasma exposures (geometric least squares mean ratios of area under the concentration–time curve extrapolated to infinity and maximum concentration) of remdesivir, GS-704277, and GS-441524 were similar in the moderate hepatic impairment group and up to 1.56-fold, 2.41-fold, and 1.48-fold higher, respectively, in the severe hepatic impairment group. Remdesivir was generally safe and well tolerated in hepatically impaired individuals, and the modest exposure increases of remdesivir and its metabolites were not associated with adverse events. Based on these findings, no dose adjustment of remdesivir is recommended for patients with mild, moderate, or severe hepatic impairment.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emapalumab in Patients With Macrophage Activation Syndrome Associated With Still's Disease: A Population Pharmacokinetic/Pharmacodynamic Analysis","authors":"Patrick Brossard","doi":"10.1111/cts.70163","DOIUrl":"https://doi.org/10.1111/cts.70163","url":null,"abstract":"<p>Macrophage activation syndrome (MAS) is a life-threatening form of secondary haemophagocytic lymphohistiocytosis (HLH) associated with rheumatic diseases, most commonly Still's disease. This study aimed to develop a population pharmacokinetic (PK)/pharmacodynamic (PD) model for emapalumab, a fully human monoclonal antibody that targets interferon-gamma (IFNγ), in patients with MAS associated with Still's disease. A two-compartment disposition model based on data from patients with primary HLH administered emapalumab (1 mg/kg every 3 days, with possible increases to 3, 6 or 10 mg/kg) was re-estimated for patients with MAS administered emapalumab (6 mg/kg, then 3 mg/kg every 3 days until day 15 and twice weekly until day 28). An exploratory population PK/PD analysis comprising patients' PD data for total IFNγ, chemokine C-X-C motif ligand 9 (CXCL9) and ferritin was performed. Emapalumab clearance was generally linear and independent of total IFNγ levels in patients with MAS (<i>n</i> = 14). Estimated baseline levels of CXCL9 (a marker of IFNγ activity), soluble interleukin-2 receptor α (sIL-2Rα; a marker of hyperinflammation) and ferritin (a clinical marker of MAS disease activity) were 8400, 6550 and 15,300 μg/L, respectively. All three PD markers responded rapidly to changes in emapalumab concentration. Emapalumab almost completely suppressed CXCL9, sIL2-Rα, and ferritin production (estimated reduction in synthesis rate: 98.3%, 87%, and 99.6%, respectively). Population PK/PD modeling indicated that emapalumab rapidly suppresses markers of hyperinflammation in patients with MAS associated with Still's disease. Emapalumab dosing regimen used in clinical trials in patients with MAS is unlikely to need adjustment.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70163","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioequivalence of Aripiprazole Oral Soluble Films and Orally Disintegrating Tablets in Healthy Participants: A Crossover Study","authors":"Ruoming Li,&nbsp;Shaojie Yang,&nbsp;Guigang Yang,&nbsp;Xingli Gu,&nbsp;Zuokai Zhang,&nbsp;Taixin Wang,&nbsp;Yunlong Tan,&nbsp;Song Chen","doi":"10.1111/cts.70142","DOIUrl":"https://doi.org/10.1111/cts.70142","url":null,"abstract":"<p>Schizophrenia is a serious mental disorder with high disability rates, and antipsychotics, especially second-generation ones like aripiprazole, are the cornerstone of treatment. As a novel formulation, oral soluble films (OSF) offer an alternative to tablets or capsules, improving patient compliance. This study aimed to assess the bioequivalence, pharmacokinetic (PK) properties, and safety of aripiprazole OSF and aripiprazole orally disintegrating tablets (ODT) in healthy Chinese participants. A single-dose, randomized, open-label, and crossover study was conducted. Participants received 10 mg of test aripiprazole OSF (Qilu Pharmaceutical) and reference aripiprazole ODT (Otsuka Pharmaceutical) under fasting and fed states. The fasting trial comprised a three-sequence, three-period design, while the fed trial comprised a two-sequence, two-period design. In the fasting trial, after single oral dosing of aripiprazole OSF (with water), aripiprazole OSF (without water), and aripiprazole ODT, C_max were 55 ± 10 ng/mL, 54 ± 10 ng/mL, and 48 ± 13 ng/mL, respectively; the AUC_0-72h were 1857 ± 377 h·ng/mL, 1823 ± 350 h·ng/mL, and 1745 ± 405 h·ng/mL, respectively. In the fed trial, after single oral dosing of aripiprazole OSF and ODT with water, the C_max were 43 ± 9 ng/mL and 43 ± 10 ng/mL, respectively; AUC_0-72h were 2024 ± 387 h·ng/mL and 1994 ± 426 h·ng/mL, respectively. In terms of bioequivalence evaluation, the 90% confidence intervals of the geometric mean ratio of the main PK parameters of aripiprazole OSF and ODT in the fasting and fed states were all within the acceptable equivalence range (80%–125%). Both formulations were well-tolerated. In conclusion, aripiprazole OSF and ODT reached bioequivalence, and aripiprazole OSF demonstrates significant potential for application in the treatment of psychiatric disorders.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70142","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Systematic Review and Meta-Analysis of Low Dose Radiation Therapy for COVID-19 Pneumonia: Learnings of 4 Years Since Pandemic","authors":"Usha Yadav,&nbsp;Balvinder Kaur Sapra","doi":"10.1111/cts.70137","DOIUrl":"https://doi.org/10.1111/cts.70137","url":null,"abstract":"<p>COVID-19 caused a worldwide pandemic resulting in break of demand–supply chain in all aspects of healthcare, high mortality rates, and a constant quest for effective treatment modalities. Based on historical and recent evidences of anti-inflammatory effects of low dose of ionizing radiation, several healthcare professionals proposed low-dose radiation therapy (LDRT) along with ongoing pharmacological treatment for COVID-19 pneumonia. A positive response in a few initial studies led to systematic trials by increasing the number of patients in the range of 0.5–1.5 Gy. However, the concerns of radiation-induced risks were also raised in parallel. In the present article, we have highlighted the basis of LDRT for COVID-19 therapy. We have reviewed the available literature, specifically for outcomes on various clinical trials carried out with LDRT. Meta-analysis was performed to identify if any survival benefits are offered by addition of LDRT over pharmacological treatment alone among COVID-19 pneumonia patients. Other clinical recovery parameters such as intubation rates, oxygenation status, anti-inflammatory response have also been compared. Overall data trends favored LDRT with standard pharmacological treatment against control cohort which received standard treatment alone at all the endpoints in majority studies. LDRT addition resulted in significantly higher odds of survival than control cohort. Among critical and/or mechanically ventilated patients, LDRT did not show any promising outcomes over the control group. In conclusion, LDRT may serve as a promising complementary treatment modality with a potential of better prognosis, provided the patient selection criteria are critically identified and implemented.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70137","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role and Challenges of Investigator-Initiated Trials in the Cell and Gene Therapy Products Boom in Mainland China","authors":"Yifan Yang,&nbsp;Lianlian Bian,&nbsp;Yuan Cheng,&nbsp;Yan Xu,&nbsp;Hui Shao,&nbsp;Jian Rao,&nbsp;Sixiang Ge,&nbsp;Jifang Gong,&nbsp;Min Jiang,&nbsp;Xiaoyu Zheng,&nbsp;Lijun Liu,&nbsp;Shihui Ma,&nbsp;Xuan Liu,&nbsp;Tao Cheng,&nbsp;Chenyan Gao","doi":"10.1111/cts.70148","DOIUrl":"https://doi.org/10.1111/cts.70148","url":null,"abstract":"<p>As cutting-edge technologies in biomedicine, cell and gene therapy (CGT) products demonstrate immense potential in treating cancer, rare diseases, and genetic disorders, thereby driving the importance of clinical research in this area. This study analyzes the growth trends and key characteristics of 1033 Investigator-Initiated Trials (IITs) conducted by mainland Chinese institutions in the CGT field. The results show that IITs have played a positive role in the early proof-of-concept of CGT products, helping to obtain preliminary safety and efficacy data, and exploring the combination of CGT products with other therapies. Additionally, this study discusses the regional distribution, therapeutic areas, and challenges faced by IITs in the development of CGT products in China. Based on these findings, policy suggestions are proposed to optimize the regulation of IITs in mainland China, such as improving regulatory frameworks and enhancing technical guidance. It is hoped that these measures will further improve the efficiency and quality of IITs, fully utilize the large patient base and abundant clinical resources, and support the development of high-quality CGT products in mainland China.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70148","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Pharmacokinetic Interaction Between Metformin and the Natural Product Goldenseal Is Metformin Dose-Dependent: A Three-Arm Crossover Study in Adults With Type 2 Diabetes","authors":"James T. Nguyen,&nbsp;Christopher M. Arian,&nbsp;Rakshit S. Tanna,&nbsp;Maxey G. Cherel,&nbsp;Matthew E. Layton,&nbsp;John R. White,&nbsp;Kenneth E. Thummel,&nbsp;Mary F. Paine","doi":"10.1111/cts.70120","DOIUrl":"https://doi.org/10.1111/cts.70120","url":null,"abstract":"<p>Pharmacokinetic drug interactions can lead to unexpected changes in plasma concentrations of the object drug, potentially increasing the risk for adverse effects and/or decreasing therapeutic efficacy. The botanical product goldenseal was previously shown to decrease metformin systemic exposure in healthy adults. This three-arm, open-label, crossover clinical study assessed the pharmacokinetic goldenseal–metformin interaction in adults with type 2 diabetes stabilized on therapeutic doses of metformin (500–2550 mg daily). The aggregate pharmacokinetic data indicated no clinically meaningful interaction as determined by the metformin area under the plasma concentration-time curve (AUC) geometric mean ratio [90% confidence interval] of 0.93 [0.86–1.01] laying within the predefined no-effect range (0.80–1.25). However, metformin AUC decreased by ~20%, 14%, and 0% after goldenseal coadministration at low (500–750 mg), moderate (1000–1500 mg), and high (2000–2550 mg) metformin doses, respectively; renal clearance and half-life remained unchanged throughout. The exploratory pharmacodynamic endpoint, HbA1c, decreased on average from 6.8% to 6.5%, regardless of the effects of goldenseal on metformin pharmacokinetics. The decreasing effect of goldenseal on metformin systemic exposure with increasing metformin dose, coupled with no changes in renal excretion and elimination half-life, indicated that both the pharmacokinetic goldenseal–metformin interaction and the nonlinear absorption of metformin are governed by saturable, intestinal transport mechanism(s). The disconnect between changes in metformin systemic exposure and therapeutic effects emphasizes the need to evaluate clinical biomarkers to comprehensively assess drug interaction risks, particularly those involving natural products. Healthcare providers may consider cautioning patients about supplementing metformin pharmacotherapy with goldenseal to avoid risks for undesired changes in glycemic control.</p><p><b>Trial Registration:</b> ClinicalTrials.gov identifier: NCT05081583</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70120","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}