Clinical therapeutics最新文献

{"title":"Safeguarding Cannabis for Medical Use: Clinical Risks, Regulatory Gaps, and the Path Toward Equitable Standards.","authors":"Shawn P Collins","doi":"10.1016/j.clinthera.2025.12.011","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.12.011","url":null,"abstract":"<p><p>Cannabis has moved into mainstream clinical use, yet the systems that should guarantee patient safety still lag. Oversight in the United States remains fragmented across states, with inconsistent thresholds, variable testing panels, and enforcement that often follows rather than prevents harm. Microbial contamination persists in regulated markets. Pathogenic Aspergillus has been detected in products that passed culture-based screens. Case reports in immunocompromised patients underscore real clinical consequences. Chemical contaminants, pesticides, heavy metals, and solvents, add cumulative risk and plausibly affect drug metabolism. State reforms have tried to tighten controls. Massachusetts required single-laboratory testing and digital certificate uploads. Those changes limited obvious lab shopping but left a fundamental flaw in place: cultivators and manufacturers still choose the samples. When sampling is compromised, even excellent laboratory work cannot protect patients. The 2025 suspension of Assured Testing Laboratories, along with recalls and lab actions in other states, shows the system's weakest points. International models demonstrate better paths. Canada uses pathogen-specific assays and broad pesticide panels, with high compliance. The European Medicines Agency has drafted pharmacopoeial standards for cannabis flos. Germany and Israel regulate cannabis as a medical product and link quality to reimbursement and distribution. My position is that U.S. policy should move to pathogen-specific molecular testing, harmonized chemical limits, and independent, regulator-controlled sampling. Equity protections are essential so safe products are accessible, not exclusive. Patients deserve cannabis regulated with the seriousness we expect for any therapeutic agent.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146092399","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":"Letters From the Field: Challenges and Opportunities in the Development of Botanical Drugs From Cannabis","authors":"Justyna Kulpa PhD,&nbsp;Schuyler A. Pruyn MS,&nbsp;George Hodgin MBA","doi":"10.1016/j.clinthera.2025.11.010","DOIUrl":"10.1016/j.clinthera.2025.11.010","url":null,"abstract":"<div><div>Cannabis and cannabis-derived products (CCDPs) have gained recognition for their therapeutic potential, driving legal and social shifts worldwide. In the United States, state-level medical cannabis programs exist alongside the federal drug development framework, which remains the gold standard for ensuring safety and efficacy. The Food and Drug Administration (FDA) botanical drug development guidance provides a structured approval pathway for plant-derived products, including CCDPs, accounting for their unique chemical complexity. Despite this guidance, significant gaps persist in preclinical and clinical data, particularly for minor cannabinoids. Development of botanical drugs from cannabis is further complicated by regulatory oversight from the Drug Enforcement Administration, which constrains the cultivation, handling, and distribution of cannabis and imposes logistical and security requirements during drug development. This article discusses the unique experience of drug developers navigating the scientific and regulatory challenges inherent in advancing CCDPs toward FDA drug approval. Collaborative efforts among federally compliant drug developers, regulatory bodies, healthcare providers, academic institutions, investors, and patients/patient advocacy groups are critical to generate rigorous, reproducible evidence to support the safe and effective use of CCDPs in medical conditions where they hold the greatest therapeutic potential. Such partnerships can advance studies that elucidate cannabinoid pharmacology, optimize dosing with rigorously characterized materials via clinically relevant routes, and identify clinical outcomes that are meaningful to patients. Advancing CCDPs through federally compliant drug development pathways will enable the translation of promising botanical therapies into safe, effective, and evidence-based treatments, ultimately informing clinical practice and benefiting patients.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 1","pages":"Pages 38-45"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800206","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":"Centering Individuals With Mental Illness as an At-Risk Group in the Era of Cannabis Legalization and Commercialization","authors":"Andrew S. Hyatt MD","doi":"10.1016/j.clinthera.2025.11.009","DOIUrl":"10.1016/j.clinthera.2025.11.009","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 1","pages":"Pages 34-37"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699981","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":"Bioequivalence and Safety Study of Ranolazine Extended-Release Tablets in Chinese Healthy Subjects Under Fasting and Fed Conditions: A Randomized, Open-Label, Single-Dose, Cross-Over, Comparative Pharmacokinetic Study","authors":"Xing Chen MM ,&nbsp;Yaming Li MM ,&nbsp;Genshan Ma PhD","doi":"10.1016/j.clinthera.2025.11.002","DOIUrl":"10.1016/j.clinthera.2025.11.002","url":null,"abstract":"<div><h3>Purpose</h3><div>The bioequivalence of the generic (Test formulation, T) and the originator (Reference formulation, R) ranolazine extended-release tablets was assessed in Chinese healthy subjects under fasting and fed conditions.</div></div><div><h3>Methods</h3><div>The study was conducted in accordance with a randomized, open, single-dose, 2-period, self-crossover design, with 36 subjects enrolled in each of the fasting and fed trials. Each subject received a 500 mg T or R tablet under fasting or fed conditions. Blood samples collected up to 48 h post-dose were determined for plasma concentrations of ranolazine by LC-MS/MS. The primary pharmacokinetic parameters were analyzed using a non-compartmental model, and geometric mean ratio (GMRs) for T/R and their 90% confidence interval (CI) were calculated for bioequivalence assessment. Adverse events (AEs) were monitored throughout, with safety assessments performed.</div></div><div><h3>Results</h3><div>The 90% CIs for the GMRs of the primary pharmacokinetic parameters (C_max, AUC_0-t, and AUC_0-∞) between the T and R administered under fasting conditions were 95.17% (85.48%–105.96%), 97.55% (87.52%–108.73%), and 94.75% (85.26%–105.30%), respectively. Similarly, under fed conditions, the 90% CIs for the GMRs of C_max, AUC_0-t, and AUC_0-∞ were 92.88% (84.25%–102.40%), 98.41% (92.66%–104.52%) and 97.60% (92.13%–103.41%), respectively. All values fell within the 80.00% to 125.00% range, thus meeting bioequivalence criteria. No serious AEs were reported during the study, indicating favorable safety and tolerability.</div></div><div><h3>Implications</h3><div>The test formulation, ranolazine extended-release tablets, demonstrated a similar safety profile to the reference formulation, Ranexa, and was shown to be bioequivalent in healthy Chinese subjects in both fasting and fed conditions.</div></div><div><h3>Clinical trial registration</h3><div>ClinicalTrials.gov, identifier: NCT07054255.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 1","pages":"Pages 88-94"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145630998","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":"KOMZIFTI (Ziftomenib)","authors":"Paul Beninger MD, MBA","doi":"10.1016/j.clinthera.2025.12.010","DOIUrl":"10.1016/j.clinthera.2025.12.010","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 1","pages":"Pages 129-130"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843596","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":"Phase 1 Study Evaluating the Effect of Food and Omeprazole-Induced Gastric pH Change on the Pharmacokinetics and Safety of Imlunestrant in Healthy Females","authors":"Amita Datta-Mannan PhD ,&nbsp;Elaine Shanks PhD ,&nbsp;Eunice Yuen PhD ,&nbsp;Yingying Guo PhD ,&nbsp;Xuejing Aimee Wang PhD","doi":"10.1016/j.clinthera.2025.10.007","DOIUrl":"10.1016/j.clinthera.2025.10.007","url":null,"abstract":"<div><h3>Purpose</h3><div>To assess the effect of low-fat food intake and the effect of a gastric acid reducing agent (omeprazole) on imlunestrant pharmacokinetics (PK), safety, and tolerability.</div></div><div><h3>Methods</h3><div>A phase 1, open-label cohort study (NCT04840888) in healthy adult females of non-childbearing potential Food effect was evaluated in cohort 1 in which, participants were randomized (1:1) to fasted/fed or fed/fasted crossover treatment sequences and received one dose of 400 mg imlunestrant once-daily in each fed (a low-fat meal; 500 calories, 13% fat) or fasted state with 4 days washout period between doses. Omeprazole’s effect was evaluated in cohort 2, in which participants received imlunestrant in fixed treatment sequence with a washout period between doses: (1) a single dose of 400 mg imlunestrant alone on Day 1, (2) no treatment between Day 2–Day 5, (3) 40 mg omeprazole alone once-daily between Day 5–8, and (4) 400 mg imlunestrant + 40 mg omeprazole on Day 9. Blood samples for PK assessments were collected for the evaluation of the areas under the concentration curve AUC_(0-96h), AUC_(0-∞), maximum observed drug concentration (C_max), time of maximum observed drug concentration (Τ_max); their geometric least squares (GLS) mean ratios were calculated. Safety assessments involved monitoring of adverse events (AEs), clinical chemistry, hematology, vital signs, 12-lead electrocardiogram, and physical examination.</div></div><div><h3>Findings</h3><div>Eight females were enrolled in cohort 1 and 10 in cohort 2. In cohort 1, PK parameters were statistically significantly increased with GLS mean ratios (90% CI): 1.99 (1.67, 2.36) in AUC_(0-96h), 2.04 (1.41, 2.94) in AUC_(0-∞), and 3.55 (2.83, 4.45) in C_max, following dosing with imlunestrant in the fed state compared to the fasted state. The change in Τ_max was not statistically significant. In cohort 2, the change in PK parameters of imlunestrant when dosed alone and in the presence of the PPI omeprazole were not statistically significant and were comparable. Imlunestrant was well tolerated, and no clinically meaningful findings were recorded in either cohort.</div></div><div><h3>Implications</h3><div>Low-fat food intake resulted in increases of ∼2-fold in AUC and ∼3.6-fold in C_max. Therefore, patients will be instructed to abstain from food consumption two hours before and one hour after taking imlunestrant. Concomitant use of imlunestrant and omeprazole displayed a low risk of drug-drug interaction, therefore imlunestrant may be taken with a proton pump inhibitor such as omeprazole. A single oral dose of 400 mg imlunestrant was generally well tolerated in healthy females regardless of food or omeprazole intake.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 1","pages":"Pages 81-87"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145581922","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":"Leukocytoclastic Vasculitis and Profound Cytopenias Following Teicoplanin Therapy: A Case Report on Glycopeptide Cross-Reactivity","authors":"Qimei Wei PhD,&nbsp;Wen Jiang MSc,&nbsp;Xinshuang Chen MSc,&nbsp;Hao Cai MSc,&nbsp;Rui Feng MSc,&nbsp;Shanshan Dong PhD","doi":"10.1016/j.clinthera.2025.11.008","DOIUrl":"10.1016/j.clinthera.2025.11.008","url":null,"abstract":"<div><h3>Purpose</h3><div>To report a case of teicoplanin-induced leukocytoclastic vasculitis with concurrent bicytopenia.</div></div><div><h3>Methods</h3><div>A 61-year-old male with penicillin allergy and postaortic valve replacement was switched from vancomycin to teicoplanin for <em>Enterococcus faecalis</em> endocarditis due to renal impairment concerns.</div></div><div><h3>Findings</h3><div>On day 9 of teicoplanin therapy, pruritic maculopapular eruptions developed alongside neutropenia (absolute neutrophil count 1.5 × 10⁹/L) and thrombocytopenia (platelets 152 × 10⁹/L). After drug discontinuation, platelet count further declined to a nadir of 5 × 10⁹/L, requiring transfusions. Clinical recovery paralleled rash resolution.</div></div><div><h3>Implications</h3><div>This case highlights the risks of glycopeptide cross-reactivity and the importance of close hematologic monitoring.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 1","pages":"Pages 121-124"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145713677","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":"Letter to the Editor Regarding “Efficacy and Safety of Simnotrelvir-Ritonavir Compared With Nirmatrelvir-Ritonavir in the Treatment of COVID-19: Real-World Evidence From a Retrospective Cohort Study During the Prevalence of the Omicron EG.5 Variant”","authors":"Hinpetch Daungsupawong PhD ,&nbsp;Viroj Wiwanitkit MD","doi":"10.1016/j.clinthera.2025.07.017","DOIUrl":"10.1016/j.clinthera.2025.07.017","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 1","pages":"Pages 125-126"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788457","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 Dangers of Practicing Recreational Regulation of Medicinal Cannabis","authors":"Jill L. Maron MD, MPH","doi":"10.1016/j.clinthera.2025.12.008","DOIUrl":"10.1016/j.clinthera.2025.12.008","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 1","pages":"Page 1"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846588","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":"Evaluation of Colorectal Cancer Incidence in the United States From 2021 to 2024 Using a National Multi-Payer Claims Database","authors":"Mallik Greene PhD, DBA, BPharm ,&nbsp;Shrey Gohil PhD ,&nbsp;Brad Stieber MS ,&nbsp;A. Burak Ozbay PhD, MBA ,&nbsp;Jorge Zapatier MD ,&nbsp;Jemel Bingham MD ,&nbsp;Joseph W. LeMaster MD, MPH ,&nbsp;Igor Stukalin MD ,&nbsp;Joseph C. Anderson MD ,&nbsp;Jordan K. Karlitz MD","doi":"10.1016/j.clinthera.2025.10.006","DOIUrl":"10.1016/j.clinthera.2025.10.006","url":null,"abstract":"<div><h3>Purpose</h3><div>Colorectal cancer (CRC) remains the second leading cause of cancer-related death in the U.S. This study aimed to evaluate national CRC incidence from 2021 to 2024 using a large, multi-payer claims database.</div></div><div><h3>Methods</h3><div>This retrospective, cross-sectional study used a national multi-payer claims database to estimate annual CRC incidence from 2021 to 2024. Adults aged 45 to 75 years were included if they had no history of CRC diagnosis from 2015 through the year prior to the given calendar year (2021, 2022, 2023, or 2024) and had at least 1 medical or pharmacy event in a 3-year window centered on that year. CRC incidence was defined as a new diagnosis claim during each study year. Annual incidence rates per 100,000 individuals were calculated and stratified by sociodemographic characteristics. Associations between CRC incidence status (new diagnosis vs. no diagnosis) and sociodemographic subgroups were assessed using Pearson’s chi-square tests.</div></div><div><h3>Findings</h3><div>From 2021 to 2024, CRC incidence declined from 136.9 to 115.9 per 100,000 among 145 to 161 million eligible individuals, with declines in those aged 50 to 64 (120.8–101.7) and 65 to 75 (203.6–162.5). In contrast, incidence among those aged 45 to 49 increased from 59.5 to 63.1 over the same period. Incidence remained higher in males than females (129.4 vs. 104.3 in 2024), and although it decreased, it remained highest among Black individuals (225.1–156.8). Medicare Advantage enrollees had the highest incidence throughout (276.8–214.0), while those with commercial insurance had one of the lowest (112.8–93.4). Regional differences narrowed from 2021 to 2024 across the Northeast, Midwest, South, and West; CRC incidence status remained significantly associated with region (Pearson’s chi-square <em>P</em> &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>Overall, CRC incidence declined from 2021 to 2024, though rising rates among adults aged 45 to 49 highlight a growing early-onset burden. Associations between CRC incidence status and age, sex, race/ethnicity, insurance type, and region were observed, suggesting disparities that may reflect underlying equity gaps in prevention.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 1","pages":"Pages 57-64"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596170","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}