Clinical therapeutics最新文献

{"title":"Implementing CYP2C19 Pharmacogenetic Testing for Personalized Antiplatelet Therapy: Findings From the QPGx-CARES Initiative","authors":"Rania Abdel-latif PhD ,&nbsp;Wadha Al Muftah MD ,&nbsp;Shaban Mohammed MD ,&nbsp;Toka AlHsson BPharmSc ,&nbsp;Daoud Al-Badriyeh PhD ,&nbsp;Radja Badji PhD ,&nbsp;Awad Al-Qahtani MD ,&nbsp;Abdul Rahman Arabi MD ,&nbsp;Said Ismail PhD ,&nbsp;Moza Al Hail BPharmSc ,&nbsp;Jassim Al Suwaidi MD","doi":"10.1016/j.clinthera.2025.12.003","DOIUrl":"10.1016/j.clinthera.2025.12.003","url":null,"abstract":"<div><h3>Purpose</h3><div>CYP2C19 loss-of-function (LoF) alleles are associated with increased cardiovascular risk in clopidogrel-treated percutaneous coronary intervention (PCI) patients. Despite the guidelines recommendation for newer P2Y12 inhibitors, clopidogrel remains widely prescribed. The study the potential impact and feasibility of implementing pharmacogenetics (PGx) testing to guide antiplatelet therapy and develop strategies for its clinical integration to improve patient management.</div></div><div><h3>Methods</h3><div>A pilot study following a prospective cohort design was conducted within the largest community healthcare provider in Qatar using point-of-care (POC) CYP2C19 genotyping in tailoring antiplatelet therapy for PCI patients. Eligible patients underwent CYP2C19 genotyping, and P2Y12 inhibitor prescriptions were adjusted based on genetic results. The study measured antiplatelet prescribing patterns and identified clinically significant gene-drug interactions.</div></div><div><h3>Findings</h3><div>Out of 376 patients tested, 283 patients received PGx-guided recommendations for anti-platelet therapy. Actionable CYP2C19 alleles were detected in 22% of those patients, prompting a change in drug therapy. PGx-guided recommendations were adopted at a rate of 80%, and CYP2C19 genotyping was a significant predictor of antiplatelet therapy adjustments. A sub-analysis of the cost impact revealed an estimated reduction of 300 QR (82.41 $) per patient annually for ACS patients who underwent PCI with stent placement.</div></div><div><h3>Implications</h3><div>This real-world study highlights the feasibility and clinical impact of CYP2C19 genotyping in guiding antiplatelet therapy for ACS and PCI patients, supporting broader PGx testing implementation in routine cardiovascular care.</div></div><div><h3>Trail registration</h3><div>HMC-IRB Registration: IRB-HMC-2021-011, IRB-MoPH Assurance: IRB-A-HMC-2019-0014. ISRCTN registration: ISRCTN15110009, <span><span>https://www.isrctn.com/ISRCTN15110009</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 2","pages":"Pages 170-178"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846586","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":"LYNKUET® (elinzanetant)","authors":"Paul Beninger MD, MBA","doi":"10.1016/j.clinthera.2025.12.006","DOIUrl":"10.1016/j.clinthera.2025.12.006","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 2","pages":"Pages 208-209"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849042","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":"Comment on “Pharmacists’ Knowledge and Perceptions of Buprenorphine at New York State Pharmacies: Identifying the Extent of Pharmacy-Level Barriers to Access Buprenorphine”","authors":"Siyi Liu","doi":"10.1016/j.clinthera.2025.11.013","DOIUrl":"10.1016/j.clinthera.2025.11.013","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 2","pages":"Pages 206-207"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773897","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":"Trending: The Critical Importance of Public Databases to Public Health","authors":"Paul Beninger MD, MBA","doi":"10.1016/j.clinthera.2026.01.005","DOIUrl":"10.1016/j.clinthera.2026.01.005","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 2","pages":"Pages 135-137"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046287","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":"Expanding Nonhormonal Options for Menopausal Vasomotor Symptoms: Clinical Impact of Elinzanetant","authors":"Renee R. Eger MD, FACOG, MSCP","doi":"10.1016/j.clinthera.2026.01.003","DOIUrl":"10.1016/j.clinthera.2026.01.003","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 2","pages":"Pages 210-212"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146092274","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":"Pharmacokinetic Equivalence of AmphosomTM, a Newly Developed Liposomal Amphotericin B, to AmbisomeⓇ","authors":"Seunghoon Han MD, PhD ,&nbsp;Dong-Seok Yim MD, PhD ,&nbsp;Sungpil Han MD, PhD ,&nbsp;Suein Choi MD, PhD ,&nbsp;Sung-Yeon Cho MD, PhD ,&nbsp;Raeseok Lee MD, PhD ,&nbsp;Dukhee Nho MD ,&nbsp;Hye-Jeong Baek MS ,&nbsp;Dong-Gun Lee MD, PhD","doi":"10.1016/j.clinthera.2025.12.009","DOIUrl":"10.1016/j.clinthera.2025.12.009","url":null,"abstract":"<div><h3>Purpose</h3><div>This study evaluated the bioequivalence of a newly developed liposomal amphotericin B (LAmB) formulation (DKF-5122, Amphosom™) relative to AmBisome^Ⓡ and mechanistically characterized the pharmacokinetic property.</div></div><div><h3>Methods</h3><div>The two-period crossover trial included a patient cohort receiving once-daily infusions for 5 days per period and a healthy-adult cohort receiving a single dose per period. Both cohorts received 3 mg/kg intravenously, and plasma concentrations of LAmB and free drug (fAmB) were analyzed. Bioequivalence in healthy adults was evaluated using conventional criteria. A joint population model was developed based on healthy-adult data, linking LAmB and fAmB through first-order liposomal release and linear disposition. Model adequacy was assessed by goodness-of-fit diagnostics, prediction-corrected visual predictive checks, and bootstrap analysis.</div></div><div><h3>Results</h3><div>Thirty-one participants contributed to the dataset (six patients and twenty-five healthy adults). In healthy adults, Test-to-Reference geometric mean ratios (90% confidence intervals) were 1.08 (1.04–1.12) for the maximum concentration of LAmB and 1.01 (0.94–1.08) for the area under the curve; for fAmB, the corresponding values were 1.00 (0.91–1.10) and 1.01 (0.95–1.07), meeting conventional bioequivalence criteria. Both LAmB and fAmB were well described by 3-compartment models, and the only formulation-related difference was a statistically significant reduction in the central compartment volume of LAmB for the Test formulation. However, this difference was not of a magnitude that would meaningfully affect the BE outcome. Covariate effects were not clinically relevant.</div></div><div><h3>Conclusions</h3><div>Amphosom™ achieved pharmacokinetic bioequivalence to AmBisome^Ⓡ, and the joint model explained the observed similarity by quantifying liposomal release and systemic disposition of LAmB and fAmB. ClinicalTrials.gov identifier: NCT05749380.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 2","pages":"Pages 186-195"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145942776","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":"Analyzing Prescription Drug to Over-the-Counter Drug Switch Rejections: Understanding Regulatory Concerns, A Global Overview","authors":"Tais Uliana MBA ,&nbsp;Zeineb Lassoued MSc ,&nbsp;Sergio Moreno Restrepo MBA ,&nbsp;Shahper Rahman MSc ,&nbsp;Sambasiva Kolati MPharm ,&nbsp;Aritz Ateka MSc ,&nbsp;Kristie Sourial MRPharmS","doi":"10.1016/j.clinthera.2025.12.012","DOIUrl":"10.1016/j.clinthera.2025.12.012","url":null,"abstract":"<div><h3>Purpose</h3><div>Prescription-to-over-the-counter (Rx-to-OTC) switch applications face significant barriers, with many experiencing rejections despite potential public health benefits. The purpose of this article was to investigate the regulatory landscape and challenges associated with Rx-to-OTC switches, focusing on the reasons behind rejections and withdrawals across various countries. By examining unsuccessful switches and identifying potential solutions, this article aimed to provide insights into improving regulatory frameworks and enhancing access to safe and effective self-care options.</div></div><div><h3>Methods</h3><div>A qualitative analysis of 19 International Nonproprietary Names spanning 10 therapeutic areas was conducted across eight countries to identify and categorize the reasons for rejection of the switch of these medicines from prescription to nonprescription status.</div></div><div><h3>Findings</h3><div>The study identified concerns leading to the rejection of Rx-to-OTC switch applications, including safety issues, challenges in diagnoses and self-management, and behavioral risks. Inconsistencies in regulatory decisions were observed across different countries.</div></div><div><h3>Implications</h3><div>The analysis identified opportunities to improve regulatory frameworks through risk-balanced approaches, innovative technologies, pharmacist-led models, and harmonized standards across regions. These opportunities could enhance access to self-care options while easing healthcare system burdens and ensuring safety.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 2","pages":"Pages 148-158"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028619","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":"Disease Severity and Healthcare Costs Associated With Chronic Kidney Disease in Patients With Systemic Lupus Erythematosus","authors":"Amy G. Edgecomb ,&nbsp;Shirley P. Huang ,&nbsp;Carlyne Averell ,&nbsp;Christopher F. Bell ,&nbsp;Bernard Rubin","doi":"10.1016/j.clinthera.2025.12.015","DOIUrl":"10.1016/j.clinthera.2025.12.015","url":null,"abstract":"<div><h3>Purpose</h3><div>Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by immune-mediated tissue injury. It frequently affects the kidneys, and lupus nephritis (LN) is the most severe manifestation affecting approximately 40% of patients with SLE. Persistent or inadequately managed LN can progress to chronic kidney disease (CKD) and kidney failure (end-stage kidney disease [ESKD]). Data on healthcare costs for patients with SLE and CKD are limited. The aim of this retrospective observational cohort study described the impact of CKD on clinical characteristics, healthcare costs and healthcare resource utilization (HCRU) among patients with SLE in the United States using claims data.</div></div><div><h3>Methods</h3><div>This retrospective, descriptive, observational cohort study (GSK Study 217378) identified patients with SLE between January 1, 2018, and December 31, 2018. Patient demographics and clinical characteristics were assessed in the 12-month baseline period preceding index (date of first SLE diagnosis [without CKD] or date of first occurrence of highest CKD stage [SLE with CKD]). HCRU and associated costs were reported for 12 months’ follow-up.</div></div><div><h3>Findings</h3><div>Of 12,114 patients with SLE included in the study (2666 with CKD; 9448 without CKD), most were female, with moderate SLE. The proportion of patients with severe disease increased with advancing CKD stage (Stage 1: 23.0%–Stage 5: 77.7%). The incidence of SLE flares, renal-related events, SLE clinical manifestations and organ involvement were numerically higher in patients with versus without CKD, and increased as CKD advanced. The mean (standard deviation [SD]) number of healthcare interactions and total healthcare costs were numerically greater among patients with CKD versus without CKD (112.5 [83.3] versus 76.9 [62.1]; $59,956 [100,785] versus $31,652 [57,781], respectively). Healthcare interactions and costs appeared to increase numerically with advancing CKD (Stage 1: 84.3 [68.7]–Stage 5: 173.7 [106.9]; Stage 1: $36,417 [56,028]–Stage 5: $152,169 [177,656], respectively). Among patients with CKD, healthcare costs were largely driven by outpatient and inpatient costs.</div></div><div><h3>Implications</h3><div>CKD contributes to a substantial economic burden in patients with SLE compared with those without CKD, highlighting the importance of effective screening and comprehensive SLE disease management to limit kidney complications and prevent progression to LN, CKD and ESKD.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 2","pages":"Pages 138-147"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028664","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":"Study of Insulin Treatment Modalities in Adults With Cystic Fibrosis-Related Diabetes After Elexacaftor-Tezacaftor-Ivacaftor Therapy","authors":"Luc Rakotoarisoa MD ,&nbsp;François Lefebvre MD ,&nbsp;Baptiste Arnouat MD ,&nbsp;Olivia Ronsin MD ,&nbsp;Raphael Chiron MD ,&nbsp;Sophie Ramel MD ,&nbsp;Bruno Ravoninjatovo MD ,&nbsp;Pauline Mulette MD ,&nbsp;Julie Mankikian MD ,&nbsp;Pascaline Priou MD ,&nbsp;Anne Sophie Balavoine MD ,&nbsp;Rébecca Hamidfar MD ,&nbsp;Sylvie Leroy MD ,&nbsp;Stéphanie Jellimann MD ,&nbsp;Laurence Kessler MD, PhD","doi":"10.1016/j.clinthera.2025.12.016","DOIUrl":"10.1016/j.clinthera.2025.12.016","url":null,"abstract":"<div><h3>Background</h3><div>Several studies have shown improvements in glucose control after initiating elexacaftor/tezacaftor/ivacaftor (ETI) in cystic fibrosis-related diabetes (CFRD) patients. However, ETI’s impact on insulin treatment remains unclear. This observational multicenter study aimed to analyze insulin treatment characteristics in adults with preexisting CFRD after ETI treatment initiation.</div></div><div><h3>Methods</h3><div>Data on diabetes treatment and continuous glucose monitoring (CGM) were retrospectively collected for 1 year before and up to 2 years after ETI treatment initiation in adults with CFRD from 13 French CF centers. We analyzed the type of insulin treatment, insulin doses, daily distribution, and CGM parameters after 1 year of ETI therapy.</div></div><div><h3>Results</h3><div>From April to December 2024<em>,</em> 107 individuals were included. The mean age was 33.2 ± 9.3 years, 49% were female, and diabetes treatment was diet for 14%, multiple daily injections for 65%, and pump for 21% of patients. After 1 year of ETI, total and bolus insulin doses decreased significantly from 0.37 IU/kg/day (0.19–0.60) to 0.30 IU/kg/day (0.17–0.49) (<em>P</em> = 0.02) and from 0.27 IU/kg/day (0.14–0.50) to 0.17 IU/kg/day (0.10–0.30), <em>P</em> = 0.0003) respectively. Among patients on a diet, 33.3% started insulin treatment, while 6.5% of patients on insulin treatment discontinued insulin. CGM parameters showed significant decreases in time below the range &lt;70 mg/dL (from 3% [1–8.5] to 2% [0–4], <em>P</em> = 0.001) and coefficient of variation (from 35% [28.7–41.7] to 33.1% [26.8–39.2], <em>P</em> = 0.001).</div></div><div><h3>Conclusions</h3><div>These findings indicate a reduction in insulin doses, particularly prandial insulin, as well as decreased glucose variability and hypoglycemia following ETI therapy in CFRD patients. Further long-term studies are needed to confirm these results.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 2","pages":"Pages 202-205"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040621","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":"The Effect of Itraconazole on the Pharmacokinetics of Vepdegestrant, a PROteolysis TArgeting Chimera Estrogen Receptor Degrader, in Healthy Adult Participants","authors":"Lana Tran PharmD ,&nbsp;Jennifer A. Winton MS ,&nbsp;Kyle T. Matschke MAS ,&nbsp;Alexandre Stouffs MD ,&nbsp;Kimberly C. Lee MBA ,&nbsp;Yuanyuan Zhang PhD ,&nbsp;Weiwei Tan PhD","doi":"10.1016/j.clinthera.2025.12.007","DOIUrl":"10.1016/j.clinthera.2025.12.007","url":null,"abstract":"<div><h3>Purpose</h3><div>Vepdegestrant (ARV-471) is an orally administered PROteolysis TArgeting Chimera estrogen receptor (ER) degrader that directly binds an E3 ligase and ER to trigger ubiquitination and subsequent proteasomal degradation of ER. Based on findings from a first-in-human phase 1/2 trial, vepdegestrant 200 mg once daily was selected as the recommended phase 3 dose and was evaluated in the phase 3 clinical study VERITAC-2 (NCT05654623) for the treatment of patients with ER-positive human epidermal growth factor receptor 2–negative breast cancer. Vepdegestrant is a substrate of cytochrome P450 (CYP)3A4 in vitro; therefore, its plasma exposure may increase when coadministered with CYP3A4 inhibitors, such as the strong index CYP3A4 inhibitor itraconazole. This study evaluated the effect of itraconazole on the pharmacokinetics (PK) and safety of vepdegestrant in healthy adults.</div></div><div><h3>Methods</h3><div>During this phase 1, open-label, 2-period, fixed-sequence study (NCT05538312), participants received 2 doses of vepdegestrant and multiple doses of itraconazole. In period 1, participants received a single dose of vepdegestrant 200 mg under fed conditions followed by a washout period of at least 10 days. In period 2, participants received itraconazole 200 mg once daily under fasted conditions on days 1–11 and a single dose of vepdegestrant 200 mg under fed conditions on day 5 with concomitant itraconazole administration. Plasma samples were collected predose and serially following each vepdegestrant dose. PK parameters calculated for vepdegestrant and its epimer metabolite, ARV-473, included area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC_inf) and maximum plasma concentration (C_max). Safety was monitored throughout the study.</div></div><div><h3>Findings</h3><div>A total of 12 healthy adult participants received vepdegestrant with (test) and without (reference) itraconazole. The vepdegestrant test/reference ratios of the adjusted geometric means (90% confidence intervals) for AUC_inf and C_max were 168.9% (157.7–180.9) and 152.2% (136.9–169.2), respectively. Similar increases in exposure were observed for ARV-473. All adverse events were mild or moderate, and no participants discontinued from the study due to adverse events.</div></div><div><h3>Implications</h3><div>Coadministration of multiple doses of itraconazole, a strong CYP3A4 inhibitor, increased vepdegestrant exposure by 69%, suggesting the involvement of CYP3A4-mediated metabolism, albeit not predominantly, in vepdegestrant elimination.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 2","pages":"Pages 179-185"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008646","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}