Drugs in Research & Development最新文献

{"title":"Development and Evaluation of Multiple-Unit Tablets for the Controlled Release of Lornoxicam.","authors":"Yang Liu, Qiong-Zhi Shi, Yanchen Wang, Ze-Chun Long, Man Han, Yuan Zeng, Xiang-Yang Xie, Hui Liu","doi":"10.1007/s40268-026-00540-1","DOIUrl":"10.1007/s40268-026-00540-1","url":null,"abstract":"<p><strong>Background and objective: </strong>Lornoxicam (LOX) is a nonsteroidal anti-inflammatory drug used for pain management but requires frequent dosing due to its short half-life. This study aimed to develop a biphasic-release multiple-unit tablet (MUT) to achieve rapid and sustained LOX release with dose flexibility.</p><p><strong>Methods: </strong>LOX-loaded extended-release (ER) pellets were prepared by fluidized-bed coating of microcrystalline cellulose cores and optimized using a Box-Behnken design. The pellets were coated with Eudragit^® RL/RS and combined with an immediate-release (IR) component to form MUTs by conventional tableting. Pellets and tablets were evaluated for physicochemical properties and in vitro drug release.</p><p><strong>Results: </strong>Optimized ER pellets showed high drug-loading efficiency (92.2 ± 3%) and good mechanical properties. Drug release from ER pellets was best described by the Korsmeyer-Peppas model, indicating Fickian diffusion. The MUTs exhibited an initial LOX release of approximately 38%, followed by sustained release for 24 h, with > 90% cumulative release. Split tablets demonstrated release profiles comparable to intact tablets (f₂ > 50).</p><p><strong>Conclusion: </strong>The developed biphasic-release MUTs provide rapid onset, sustained LOX delivery, and reliable dose flexibility, representing a promising oral formulation for LOX therapy.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"51-70"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13076759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147436996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to \"Treatment Outcomes with Lanadelumab Every Two Weeks and Garadacimab Are Very Similar in Patients with Hereditary Angioedema\".","authors":"Imtiaz A Samjoo","doi":"10.1007/s40268-026-00536-x","DOIUrl":"10.1007/s40268-026-00536-x","url":null,"abstract":"","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"35-37"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13076817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical Evaluation of AHT-102, a CLDN18.2 × CD3 Bispecific Antibody: Pharmacokinetics, Anti-Tumor Efficacy, Tissue Distribution, and Safety Profile.","authors":"Huilun Chu, Guili Xu, Yunlong Liu, Niliang Qian, Yanchuan Li, Yujie Liu, Xiujie Pan, Xin Gao, Lun Ou, Junping Lv, Haifeng Song","doi":"10.1007/s40268-026-00535-y","DOIUrl":"10.1007/s40268-026-00535-y","url":null,"abstract":"<p><strong>Background and objectives: </strong>Claudin18.2 (CLDN18.2) is a promising therapeutic target overexpressed in various tumor tissues. While CD3-engaging bispecific antibodies show great potential, their clinical application is often limited by poor efficacy in solid tumors and significant safety risks, such as cytokine release syndrome (CRS). The objective of this study was to comprehensively evaluate the preclinical anti-tumor efficacy, pharmacokinetics, tissue distribution, and safety profile of AHT-102, a novel Fc-free CLDN18.2 × CD3 bispecific antibody with a low-affinity CD3 arm, to determine its potential for clinical development.</p><p><strong>Methods: </strong>This study evaluated the anti-tumor efficacy of AHT-102 in CLDN18.2-positive gastric cancer mouse models (NUGC4-CLDN18.2). We further assessed its pharmacokinetic characteristics, quantitative tissue distribution using ¹²⁵I-labeling, and long-term toxicity in human CD3EDG transgenic mice.</p><p><strong>Results: </strong>AHT-102 (0.1, 0.3, and 1 mg/kg) demonstrated significant dose-dependent anti-tumor effects, with tumor weight inhibition reaching 51% at the 1-mg/kg dose. Pharmacokinetic analysis in CD3EDG mice revealed linear characteristics with refined terminal half-lives of 0.762 h, 3.05 h, and 4.25 h for doses of 0.1, 0.5, and 2.5 mg/kg, respectively. Tissue distribution studies confirmed superior targeting specificity; the tumor-to-muscle ratio exceeded 15, and the molecule successfully bypassed the 'T-cell sink' by showing lower accumulation in the lymph nodes compared with the tumor. In vitro, AHT-102 did not induce target-independent cytokine release from peripheral blood mononuclear cells (PBMCs). The maximum tolerated dose (MTD) in human CD3EDG mice reached 13.65 mg/kg, a 136.5-fold margin over the projected clinical starting dose. Observed gastric tissue damage was dose-dependent and reversible upon drug discontinuation.</p><p><strong>Conclusions: </strong>AHT-102, a novel Fab-like bispecific antibody, achieves an optimized therapeutic balance through its low-affinity CD3 arm and Fc-free format. It demonstrates significant anti-tumor efficacy and exceptional targeting specificity while avoiding systemic immunotoxicity typically associated with CD3-targeting agents. These findings provide a robust scientific rationale for the clinical translation of AHT-102 in patients with CLDN18.2-positive cancers.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"39-50"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13076708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147291539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics and Bioequivalence Evaluation of Piracetam Tablet: A Randomized, Single-Dose, Two-Period, Crossover Study in Healthy Chinese Participants Under Fasting and Fed Conditions.","authors":"Hegui Yan, Ming Zhou, Zhixiang Pan, Yu Peng, Jie Wang, Xiuwen Li, Yafang Xie, Qianying Liu, Cuiping Huang, Qiuhong Wang, Guan Liu","doi":"10.1007/s40268-026-00541-0","DOIUrl":"10.1007/s40268-026-00541-0","url":null,"abstract":"<p><strong>Background: </strong>Piracetam, a nootropic drug, is widely used for treating cognitive impairments. However, pharmacokinetic and bioequivalence data for piracetam formulations in the Chinese population are limited. This study was conducted to evaluate the pharmacokinetics and bioequivalence of a newly developed generic piracetam tablet compared with the reference product (Nootropyl^®) in healthy Chinese participants under fasting and fed conditions.</p><p><strong>Methods: </strong>A randomized, open-label, single-dose, two-period, two-sequence crossover study was conducted in healthy Chinese participants under fasting and fed conditions. Healthy participants received a single oral dose of piracetam 800 mg as either the test or reference formulation, followed by a 7-day washout period. Plasma piracetam concentrations were determined using a validated high-performance liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters, including maximum plasma concentration (C_max), area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC_0-t), and area under the plasma concentration-time curve extrapolated to infinity (AUC_0-∞), were calculated using non-compartmental analysis. Bioequivalence was assessed by calculating the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) for C_max, AUC_0-t, and AUC_0-∞.</p><p><strong>Results: </strong>56 participants were enrolled, with 28 participants completing each study under fasting and fed conditions. Under fasting conditions, the 90% confidence intervals (CIs) of the GMRs for C_max, AUC_0-t, and AUC_0-∞ were 98.53%, 98.40%, and 98.49%, respectively. Under fed conditions, the corresponding 90% CIs were 99.31%, 99.03%, and 99.01%. All values were within the predefined bioequivalence acceptance range of 80-125%. Food intake reduced the rate of absorption, as indicated by a lower C_max and delayed time to maximum concentration (T_max), without affecting the extent of absorption. Both formulations were well tolerated, and no serious adverse events were reported.</p><p><strong>Conclusions: </strong>The test piracetam tablet was demonstrated to be bioequivalent to the reference formulation with respect to the rate and extent of absorption under both fasting and fed conditions in healthy Chinese participants. The comparable safety and tolerability profiles support the clinical interchangeability of the generic and reference piracetam formulations.</p><p><strong>Clinical trial registration: </strong>CTR20213027.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"71-81"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13076839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147482364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arylpiperazine Derivative NAF19 Inhibits Prostate Cancer Activity and Its Molecular Mechanisms.","authors":"Hua Jiang, Mingzhen Xu, Songsong Jiang, Weiqiang Huang","doi":"10.1007/s40268-026-00542-z","DOIUrl":"10.1007/s40268-026-00542-z","url":null,"abstract":"<p><strong>Background and objectives: </strong>Androgen deprivation therapy (ADT) remains the primary treatment for advanced prostate cancer. However, most patients relapse within 18-24 months, progressing to castration-resistant prostate cancer (CRPC) which is currently incurable. Our preliminary studies identified the arylpiperazine derivative NAF19 as a promising therapeutic agent against prostate cancer, though its precise mechanisms remained unclear. This study aims to systematically evaluate the antitumor effects of NAF19 in prostate cancer cells and elucidate its molecular mechanisms, with a focus on its multi‑target inhibition of the AR/AR‑Vs signaling pathway and key survival pathways.</p><p><strong>Methods: </strong>To evaluate the effects of NAF19 on prostate cancer cell growth, we treated a panel of prostate cancer cell lines (LNCaP, C4-2, 22Rv1, DU145, and PC-3) representing both androgen-sensitive and castration-resistant phenotypes (including AR-expressing and AR-null subtypes) with varying concentrations of NAF19 for 72 h. Cell viability and sensitivity were subsequently assessed using the CCK-8 assay. In LNCaP and 22Rv1 cells, we further performed qRT-PCR to analyze the mRNA expression levels of AR/AR-Vs and their downstream target genes (PSA and UBE2C), flow cytometry to determine cell cycle distribution, and western blotting to examine the levels of cleaved PARP, antiapoptotic Bcl-2 family proteins, phosphorylated AKT (at Ser473 and Thr308), phosphorylated ERK, phosphorylated S6, as well as total AR and AR-V7. To assess the impact of NAF19 on tumor cell metastatic potential and proliferation, transwell migration and invasion assays, along with EdU incorporation assays, were conducted. Furthermore, a luciferase reporter assay was carried out to evaluate the transcriptional activity of the androgen receptor (AR).</p><p><strong>Results: </strong>NAF19 exhibited growth-inhibitory effects across all five prostate cancer cell lines. It significantly suppressed AR/AR-Vs downstream gene expression, induced G1-phase cell cycle arrest in 22Rv1 cells, and reduced anti-apoptotic Mcl-1 protein levels while activating apoptosis. NAF19 dose-dependently induced PARP cleavage; NAF19 significantly reduced the phosphorylation levels of AKT (at T308 and S473 sites), ERK, and S6. Functional assays confirmed marked suppression of migration, invasion, and proliferation in NAF19-treated cells.</p><p><strong>Conclusions: </strong>The novel arylpiperazine derivative NAF19 exerts multi-targeted antitumor effects by concurrently inhibiting AR/AR-Vs signaling pathways and activating apoptotic cascades, thereby potently suppressing the migratory, invasive, and proliferative capacities of prostate cancer cells.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"117-128"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13076722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147610397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acknowledgement to Referees.","authors":"","doi":"10.1007/s40268-025-00533-6","DOIUrl":"https://doi.org/10.1007/s40268-025-00533-6","url":null,"abstract":"","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145656155","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 Study of Bedaquiline and Sirturo^® in Healthy Chinese Subjects Under Fasting and Postprandial Conditions: A Randomized, Open-Label, Single-Dose, Crossover Trial.","authors":"Yixuan Li, Yi Wu, Shufan Cai, Xiangxin Huang, Lijun Ye, Lin Wang, Yingying Zhang, Ying Wang, Xuexia Tao","doi":"10.1007/s40268-025-00525-6","DOIUrl":"10.1007/s40268-025-00525-6","url":null,"abstract":"<p><strong>Background and objective: </strong>Multidrug-resistant tuberculosis remains a major global health challenge, and bedaquiline has become an essential drug for its treatment. However, the high cost of the originator product Sirturo^® limits accessibility, underscoring the need for affordable generic drugs supported by bioequivalence studies. The aim of this study was to evaluate the bioequivalence of bedaquiline fumarate tablets manufactured by Zhejiang Haizheng Pharmaceutical Co., Ltd. with the reference product Sirturo^® under fasting and postprandial conditions in healthy Chinese subjects and to assess their pharmacokinetic profile and safety to support generic drug registration in China.</p><p><strong>Methods: </strong>This study comprised a single-dose, open-label, randomized, crossover trial that was independently conducted under two conditions: fasting and postprandial. All subjects were randomized to receive the single-dose subject formulation and the reference formulation in two separate cycles. Plasma samples were collected at multiple timepoints after dosing and bedaquiline concentrations were determined by a validated ultra-performance liquid chromatography-tandem mass spectrometry method. Key pharmacokinetic parameters including maximum plasma concentration and area under the plasma concentration-time curve from time 0 to 72 h were calculated using a non-atrial model and bioequivalence was assessed using analysis of variance and 90% confidence intervals.</p><p><strong>Results: </strong>A total of 40 cases were included in the fasting group and 50 healthy subjects in the postprandial group. The geometric mean ratio of the single-dose subject formulation to the reference formulation within both groups fell within the 80.00-125.00% bioequivalence range for the 90% confidence interval of maximum plasma concentration to area under the plasma concentration-time curve from time 0 to 72 h. Overall drug exposure levels (area under the plasma concentration-time curve) were higher in the postprandial state than in the fasting state, but the subject formulation remained consistent with the reference formulation. All subjects completed the study and no serious adverse events were observed.</p><p><strong>Conclusions: </strong>Bedaquiline fumarate tablets of Zhejiang Haizheng Pharmaceutical Co., Ltd. showed good bioequivalence and tolerability with Sirturo^® under fasting and postprandial conditions, which supports its use as a generic drug in the treatment of multidrug-resistant tuberculosis.</p><p><strong>Clinical trial registration: </strong>ChiCTR2500105414.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"321-331"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12756197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145423322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Ulinastatin in Post-traumatic Sepsis: A Randomized Controlled Trial.","authors":"Ao Yang, Rui Liu, Kongbo Lv, Weijun Chen, Mengfei Han, Zhizhou Yang","doi":"10.1007/s40268-025-00524-7","DOIUrl":"10.1007/s40268-025-00524-7","url":null,"abstract":"<p><strong>Background and objective: </strong>Post-traumatic sepsis is associated with high mortality and limited treatment options. This study aimed to evaluate the safety and efficacy of ulinastatin in adult patients with post-traumatic sepsis, assess its potential as a therapeutic option, and provide a foundation for future large-scale trials.</p><p><strong>Methods: </strong>A single-blind, randomized controlled trial was conducted involving 60 patients treated at the Eastern Theater General Hospital from October 2022 to June 2024. The primary endpoint was 28-day all-cause mortality. Secondary endpoints included the Sequential Organ Failure Assessment (SOFA) score, C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT) levels, Activities of Daily Living (ADL) score, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, ICU length of stay, duration of mechanical ventilation, and other laboratory indicators.</p><p><strong>Results: </strong>No statistically significant difference was observed in 28-day mortality between the ulinastatin and control groups (p > 0.05). However, the ulinastatin group exhibited significantly shorter ICU and hospital stays compared with the control group (p < 0.05), while the duration of mechanical ventilation showed no significant difference (p > 0.05). The ulinastatin group demonstrated significant improvements in CRP, IL-6, PCT levels, as well as SOFA and APACHE II scores (p < 0.05). Safety evaluations revealed a significant reduction in ALT and AST levels in the ulinastatin group (p < 0.05), with no serious adverse events reported.</p><p><strong>Conclusion: </strong>While the 28-day mortality rate did not differ significantly between the two groups, ulinastatin was associated with shorter ICU and hospital stays, improvements in inflammatory markers and organ function, and demonstrated a favorable safety profile.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"333-341"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12756202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145446224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Omadacycline Pharmacokinetics: Characteristics, Contributing Factors, and Clinical Significance.","authors":"Huan Sun, Xiaoli Hou, Qiuzhen Zhu, Juan Liu, Qiaoli Zhai, Kourong Shi","doi":"10.1007/s40268-025-00531-8","DOIUrl":"10.1007/s40268-025-00531-8","url":null,"abstract":"<p><p>Omadacycline is a novel tetracycline with a wide range of antibacterial activity. A comprehensive understanding of the factors influencing its metabolic processes is essential to optimize its therapeutic benefits and minimize any potential negative effects. It was found that the metabolism of omadacycline does not rely on UDP-glucosyltransferase or cytochrome P450 enzymes, which gives it a clear advantage in terms of drug interactions, bioavailability, and metabolic stability. The review offers a thorough analysis of the many elements influencing the pharmacokinetics of omadacycline, including its intrinsic properties, individual differences, dietary influences, and possible drug interactions. To achieve maximum efficacy and safety in clinical practice, a thorough understanding of the pharmacokinetic properties of omadacycline is essential, which helps to better customize dosing regimens and maximize therapeutic outcomes.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"289-307"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12756217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145726897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics, Pharmacodynamics, and Safety of ET-26 in Subjects with Mild to Moderate Renal Impairment.","authors":"Fan Yang, Chao-Zhuang Shen, Pan-Pan Ye, Wen-Shuo Lv, Li-Ze Li, Jie Shao, Lei Diao, Bo-Wen Ke, Yi Zheng, Xiao-Ran Yang, Wei Zhao","doi":"10.1007/s40268-025-00528-3","DOIUrl":"10.1007/s40268-025-00528-3","url":null,"abstract":"<p><strong>Background and objectives: </strong>ET-26 is a novel etomidate analog with reduced adrenal suppression. This study evaluated its pharmacokinetics (PK), pharmacodynamics (PD), and safety in subjects with mild to moderate renal impairment.</p><p><strong>Methods: </strong>In this phase I trial, 24 subjects (normal renal function, mild renal impairment, moderate renal impairment; n = 8/group) received a single intravenous bolus ET-26 dose. PK parameters (C_max, AUC_0-∞, CL), urinary excretion, PD (time to unconsciousness, area under the curve [AUC] of the Bispectral Index [BIS]), and safety were assessed.</p><p><strong>Results: </strong>Systemic exposure (AUC_0-∞) differed by < 16% between renal impairment and normal groups (geometric mean ratios: 84.70-86.85%). C_max was ~ 46% lower in renal impairment groups, but PD responses were comparable. Renal clearance was minimal (CL_r ≤ 0.0085 L/h; urinary excretion ≤ 0.02%) with no correlation between estimated glomerular filtration rate (eGFR) and PK parameters. Safety profiles were similar across groups; mild myoclonus (25% per cohort) was the most common adverse event. No renal impairment-specific safety concerns emerged.</p><p><strong>Conclusion: </strong>Mild-to-moderate renal impairment minimally affects ET-26 exposure or efficacy due to predominant non-renal elimination. No dosage adjustment is needed for ET-26 0.8 mg/kg in these patients. However, patients with severe renal impairment or those receiving dialysis were not studied, and dedicated investigations are required before extrapolating dosing recommendations to these populations.</p><p><strong>Trial registration: </strong>CDE Clinical Trial Registry CTR20233783. Registered on 23 November 2023. http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"387-396"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12756201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145764226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}