Drugs in Research & Development最新文献

{"title":"Establishment of a Vancomycin Population Pharmacokinetic Model for Pediatric Patients Based on the Non-Linear Mixed-Effects Model.","authors":"Biao Yu, Kangkang Mei, Didi Zhan, Qi Tang, Heping Cai, Runcong Zhang","doi":"10.1007/s40268-025-00523-8","DOIUrl":"10.1007/s40268-025-00523-8","url":null,"abstract":"<p><strong>Background and objectives: </strong>Vancomycin (VCM) pharmacokinetic parameters vary widely between individuals. Existing models developed domestically and internationally may not apply universally because of differences in patient populations and testing methodologies. Therefore, the present study aimed to address the clinical challenge of optimizing individualized VCM dosing in pediatric patients at the study institution by developing a VCM population pharmacokinetic model and identifying key factors influencing VCM clearance, thereby providing a reference for safe and effective clinical dosing strategies.</p><p><strong>Methods: </strong>Data regarding 124 effective VCM concentrations and 100 pediatric patients who received intravenous VCM were retrospectively collected. We used a non-linear mixed-effects model with forward inclusion and backward elimination to create the final VCM population pharmacokinetic model. The model was internally validated using bootstrapping, goodness of fit, and visual predictive check. The Monte Carlo method was used to simulate the range of trough concentrations in pediatric patients with renal insufficiency and normal function under different dosing regimens.</p><p><strong>Results: </strong>A one-compartment model adequately described the pharmacokinetic behavior of VCM in vivo. The typical values of clearance and volume of distribution were 8.22 L/h and 113 L, respectively. Renal function and body weight were the most important factors affecting the clearance of VCM. The model was validated as stable and reliable.</p><p><strong>Conclusions: </strong>The VCM population pharmacokinetic model established during this study can assist physicians with the development and optimization of dosing regimens for pediatric patients.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"309-320"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12756205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139253","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":"Safety, Tolerability, Pharmacokinetics, and Viral Pharmacodynamics of the Monoclonal Antibody Sotrovimab Administered via Intramuscular Injection in Participants with Early, Mild-to-Moderate COVID-19: A Randomized Clinical Trial.","authors":"Anil Gupta, Maria Teresa Perez-Rodríguez, Yaneicy Gonzalez-Rojas, Moti Ramgopal, Almena Free, Jennifer Han, Jennifer Moore, Naomi Givens, Phillip J Yates, Jill T Walker, Mary Beth Connolly, Gretja Schnell, Varsha Imber, Rabia Anselm, Lindsay Winograd, Scott Segal, Stephen Harrison, Andrew Skingsley, Melissa Aldinger, Amanda Peppercorn, Jaynier Moya","doi":"10.1007/s40268-025-00529-2","DOIUrl":"10.1007/s40268-025-00529-2","url":null,"abstract":"<p><strong>Background and objectives: </strong>New coronavirus disease 2019 (COVID-19) therapeutics, including intramuscular (IM) formulations, may increase patient access. In COMET-TAIL, sotrovimab 500 mg IM was non-inferior to 500 mg intravenous (IV) in reducing the risk of COVID-19 progression; however, 250 mg IM was associated with more hospitalizations, despite similar viral load (VL) reductions to 500 mg IM.</p><p><strong>Methods: </strong>COMET-PEAK was a randomized, three-part study to assess safety, tolerability, and viral pharmacodynamics of sotrovimab in adults with early, mild-to-moderate COVID-19. Parts B/C evaluated sotrovimab 500-mg IV infusion versus 500-mg or 250-mg IM injection. The primary objective was to compare virologic response of sotrovimab IM versus IV (mean area under the curve from day 1 to day 8 [AUC_D1-8] of severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] VL); 90% confidence interval (CI) limits of 0.5-2.0 indicated equivalence.</p><p><strong>Results: </strong>Parts B/C included 167 and 157 participants, respectively. Median age range was 42-47 years, and approximately 50% of participants had one or more risk factor for severe disease. The primary objective was met: the ratio of geometric mean VL AUC_D1-8 of sotrovimab IM versus IV was 1.04 (90% CI 0.98-1.09; Part B) and 1.02 (90% CI 0.94-1.11; Part C). No new safety signals emerged for sotrovimab; IM administration was well tolerated, with few injection-site reactions.</p><p><strong>Conclusions: </strong>Both sotrovimab IM doses were equivalent to 500 mg IV with respect to SARS-CoV-2 VL change. IM administration was safe and well tolerated. The validity of VL as a biomarker for COVID-19 progression warrants further study.</p><p><strong>Clinical trial registration: </strong>NCT04779879 (date of first registration: March 3, 2021), https://classic.</p><p><strong>Clinicaltrials: </strong>gov/ct2/show/NCT04779879 .</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"353-365"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12756207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145589723","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":"Bioequivalence of Two Perampanel Oral Suspension Formulations in Healthy Subjects: A Randomized Crossover Study.","authors":"Aya M AbdelMagid, Kamal A Badr, Mamdouh R Rezk","doi":"10.1007/s40268-025-00526-5","DOIUrl":"10.1007/s40268-025-00526-5","url":null,"abstract":"<p><strong>Background and objective: </strong>Perampanel has been approved for the adjunctive treatment of partial-onset seizures and primary generalized tonic-clonic seizures. The oral suspension formulation benefits patients who have difficulty swallowing tablets. The unavailability of an affordable generic perampanel oral suspension formulation increased the need for a cheaper bioequivalent alternative to the marketed reference product. The study aimed to assess the bioequivalence of two formulations of perampanel oral suspension (0.5 mg/mL) administered under fasting conditions focusing on providing a cost-effective and accessible alternative to current formulations.</p><p><strong>Methods: </strong>This was an open-label, two-period, two-sequence, crossover, bioequivalence study conducted under fasting conditions. Healthy subjects were randomized to receive single doses of perampanel oral suspension (12 mg), Lepsiramp and Fycompa^® separated by a 6-week washout period. The maximum concentration and area under the concentration-time curve up to 72 h were the primary pharmacokinetic parameters used to assess bioequivalence.</p><p><strong>Results: </strong>The geometric mean ratio of test to reference formulations and 90% confidence interval were 109.55 (99.49-120.64) for maximum concentration and 98.15 (90.68-106.23) for the area under the concentration-time curve up to 72 h_, which were within the 80-125% bioequivalence range. The adverse events were mild headache and dizziness.</p><p><strong>Conclusions: </strong>The two oral suspension formulations were bioequivalent, safe, and well tolerated. This provides a beneficial affordable alternative for patients requiring non-tablet oral formulations.</p><p><strong>Clinical trial registration: </strong>The ClinicalTrials.gov registration number is NCT06969963, retrospectively registered on 13 May, 2025.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"343-351"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12756199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145543488","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":"Safety, Tolerability and Pharmacokinetics of a High-Dose, Rapid-Infusion Monoclonal Antibody: Phase I Results for Intravenous Sotrovimab 3000 mg.","authors":"Yasmin Sánchez-Pearson, Jennifer Moore, Jerzy Daniluk, Sookti Bhangu, Sergio Parra, Asma El Zailik, Prosenjit Sarkar, Alicia Aylott, Farai Moyo, Amanda Peppercorn, Andrew Skingsley","doi":"10.1007/s40268-025-00530-9","DOIUrl":"10.1007/s40268-025-00530-9","url":null,"abstract":"<p><strong>Background and objectives: </strong>The emergence of severe acute respiratory syndrome coronavirus 2 variants against which sotrovimab has lower in vitro neutralisation activity has led to the exploration of higher (> 500-mg intravenous) doses. This study evaluated the safety, tolerability and pharmacokinetics of intravenous sotrovimab 3000 mg.</p><p><strong>Methods: </strong>We conducted a phase I, open-label, single-arm study in healthy adults. Participants were administered a single 3000-mg dose of intravenous sotrovimab (100 mg/mL) over 60 min (50 mg/min). Adverse events, serious adverse events and adverse events of special interest were assessed through week 35. Sotrovimab pharmacokinetics were evaluated through week 24.</p><p><strong>Results: </strong>Of 100 participants enrolled, 98 received sotrovimab (median age 42.5 [range 18-64] years; 52% male; mean body mass index 25.25 kg/m²) and 96 completed the study. Overall, 37% (n = 36/98) of the participants reported adverse events, five of which were considered to be treatment related. The most common type of event was infection (13%; n = 13/98) with upper respiratory tract infection (9%; n = 9/98) being frequent. Two Grade 1 adverse events of special interest were reported. There were no serious adverse events, deaths or adverse events leading to discontinuation. Pharmacokinetic results were in line with expectations for this dose of sotrovimab, assuming linear dose-proportional pharmacokinetics, based on the population pharmacokinetic model of sotrovimab.</p><p><strong>Conclusions: </strong>Intravenous sotrovimab 3000 mg, administered over 60 min, was generally well tolerated by healthy volunteers, with a low incidence of adverse events and adverse events of special interest, no documented serious adverse events and no adverse events leading to discontinuation. Pharmacokinetic results were in line with expectations for a 3000-mg dose, assuming linear dose-proportional pharmacokinetics.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov NCT05280717; date of registration 4 March, 2022.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"367-376"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12756206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145649912","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":"Multiple-Dose Up-Titration Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Omecamtiv Mecarbil in Healthy Chinese Subjects.","authors":"Xuening Li, Hui Li, Hongrong Xu, Fei Yuan, Hanjing Chen, Chao Liu, Mengjie Yang, Jing Li, Lei Sheng","doi":"10.1007/s40268-025-00532-7","DOIUrl":"10.1007/s40268-025-00532-7","url":null,"abstract":"<p><strong>Background and objectives: </strong>This phase I study was designed to evaluate the safety, tolerability, and pharmacokinetics of omecamtiv mecarbil with multiple oral doses at 25 mg twice daily, followed by titration to either 37.5 or 50 mg twice daily in healthy Chinese participants.</p><p><strong>Methods: </strong>Fifty healthy participants were enrolled and randomly assigned into three groups: Group A (20 subjects) received omecamtiv mecarbil 25 mg in period 1 and either 37.5 mg or 25 mg in period 2; Group B (20 subjects) received omecamtiv mecarbil 25 mg in period 1 and either 50 mg or 25 mg in period 2; and Group C (10 subjects) received a placebo in both periods.</p><p><strong>Results: </strong>The pharmacokinetics of omecamtiv mecarbil were well characterized in healthy Chinese participants. Across all subgroups, the mean terminal elimination half-life ranged from 18.3 to 21.3 h. Mean accumulation ratios of area under the curve from time 0 to 12 h ranged from 4.54 to 5.01 in period 1 and 2. The mean maximum observed concentration/plasma concentration before dosing ratios varied between 1.23 and 1.31 on days 8 and 34 across subgroups. No subjects experienced serious adverse events. The most frequently reported adverse events were an increased blood creatine kinase levels (12.5% of subjects in the omecamtiv mecarbil group, 10% in the placebo group), increased blood glucose levels (7.5%, 0), and bradycardia (10%, 0).</p><p><strong>Conclusions: </strong>Omecamtiv mecarbil was well tolerated at the dose levels of 25-50 mg in healthy Chinese participants according to a pharmacokinetic-based titration scheme. Exposure of omecamtiv mecarbil was dose proportional, and no dose-related trends were observed in treatment-emergent adverse events.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"377-386"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12756200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710119","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":"Effect of Severe Renal Impairment on Dordaviprone (ONC201) Pharmacokinetics.","authors":"Shamia L Faison, Joelle Batonga, Thangam Arumugham, Angela Bartkus, Marion E Morrison, Mark J Mullin, Tim Tippin, Odin Naderer","doi":"10.1007/s40268-025-00520-x","DOIUrl":"10.1007/s40268-025-00520-x","url":null,"abstract":"<p><strong>Background and objective: </strong>Dordaviprone (ONC201) is a novel small molecule with antitumor effects in patients with glioma. The major elimination pathway of dordaviprone is metabolism via cytochrome P450 (CYP) 3A4. This study was designed to assess the effect of severe renal impairment (RI) on dordaviprone pharmacokinetics.</p><p><strong>Methods: </strong>Eight participants with severe RI and eight participants matched for age, body mass index, and sex, with normal renal function, received a single oral 375-mg dose of dordaviprone. Plasma and urine samples were analyzed for dordaviprone using validated liquid chromatography tandem mass spectrometry methods. Plasma and urine pharmacokinetics, plasma protein binding, and safety profiles were evaluated.</p><p><strong>Results: </strong>Dordaviprone exposure was increased in participants with severe RI. Geometric mean ratios (90% confidence intervals) of the severe RI cohort compared with the healthy matched cohort were 1.13 (0.92-1.39), 1.48 (0.98-2.23), and 1.47 (0.97-2.21), for maximum concentration (C_max), area under the plasma concentration-time curve from time zero to time of last measurable plasma concentration (AUC_last), and AUC from time zero to infinity (AUC_inf), respectively. Renal clearance of dordaviprone was negligible and similar in both cohorts. Plasma protein binding was similar in both cohorts, leading to similar increases in unbound dordaviprone C_max and AUC in severe RI versus healthy participants. All dordaviprone-related adverse events were mild, occurring in 50% of participants with severe RI and 37.5% of healthy matched participants.</p><p><strong>Conclusions: </strong>Despite its minimal renal clearance, dordaviprone geometric mean AUC was increased by ~50% in severe RI participants, suggesting CYP3A4 activity may have been suppressed in these participants. The results of this study will be used to inform dordaviprone dosing in patients with RI.</p><p><strong>Trial registration number: </strong>ACTRN12622000405718; Registered on March 9, 2022. Key Points Dordaviprone is a small molecule drug candidate for the treatment of glioma and is eliminated by non-renal mechanisms. In this clinical trial performed in severely renal-impaired participants, dordaviprone plasma concentrations were increased relative to those observed in healthy participants. This result suggests that the metabolic enzyme activity of CYP3A4 was reduced in severely renal-impaired participants.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"253-261"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144762090","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":"Bioequivalence Study of Two Formulations of Flunarizine Hydrochloride Capsules in Healthy Chinese Subjects Under Fasting and Fed Conditions.","authors":"Yinglin Yang, Jiejing Kai, Duo Lv, Huili Zhou, Yan Yu, Jianzhong Shentu, Guolan Wu","doi":"10.1007/s40268-025-00521-w","DOIUrl":"10.1007/s40268-025-00521-w","url":null,"abstract":"<p><strong>Background and objectives: </strong>Flunarizine, a selective calcium channel blocker with vasodilatory and neuroprotective effects, is a mainstay for migraine prophylaxis and vertigo management. This study aimed to compare the bioequivalence, pharmacokinetics, and safety of test and reference flunarizine hydrochloride capsules after a single oral dose under fasting/fed conditions.</p><p><strong>Methods: </strong>A randomized, open-label, two-formulation, single-dose, two-period crossover bioequivalence study was conducted under fasting and fed conditions. Eligible healthy Chinese subjects received a single 5-mg dose of the test or reference flunarizine hydrochloride capsules, followed by a 21-day washout interval between periods. Blood samples were collected up to 36 h post-dose. Pharmacokinetic parameters were calculated using noncompartmental methods, and bioequivalence was assessed via geometric mean ratios of the test/reference for primary pharmacokinetic parameters, along with 90% confidence intervals. Tolerability was evaluated during the entire study period.</p><p><strong>Results: </strong>Twenty-four volunteers completed the fasting study, while 42 volunteers completed the fed study. The test formulation demonstrated bioequivalence to the marketed formulation, with 90% confidence intervals for geometric mean ratios of peak plasma concentration (fasting: 97.38-106.57%; fed: 92.71-109.58%), area under the curve from time 0 to 36 h (fasting: 98.20-108.09%; fed: 93.79-100.81%), and AUC from time 0 to infinity (fasting: 97.88-107.30%; fed: 93.63-100.53%), all within equivalence limits of 80.00-125.00%. High-fat meals delayed the time to maximum concentration by 2.5 h and increased exposure by 20%. Both the test and reference formulations were well tolerated, and no serious adverse events related to the study drug were reported during the study.</p><p><strong>Conclusions: </strong>This study confirmed that test and reference flunarizine hydrochloride capsules were bioequivalent under fasting and fed conditions.</p><p><strong>Clinical trial registration: </strong>ChiCTR1900026713.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"275-284"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975376","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":"A Bioequivalence Study of Recombinant Human Follicle-Stimulating Hormone Injection Versus Recombinant Human Follitropin For Injection in Healthy Chinese Adult Women.","authors":"Jigang Zhang, Mingjian Zhang, Wenyuan Xue, Yixin Zha, Shujing Jin, Tianhong Luo, Ying Ding, Weiwei Gao, Xueying Ding, Xiaoyan Zhu","doi":"10.1007/s40268-025-00513-w","DOIUrl":"10.1007/s40268-025-00513-w","url":null,"abstract":"<p><strong>Background and objective: </strong>This study aimed to evaluate the bioequivalence of a novel prefilled recombinant human follicle-stimulating hormone (rh-FSH) injection (GenSci008) compared with the existing rh-FSH for injection (Jinfollin^®) in healthy Chinese adult women.</p><p><strong>Methods: </strong>This open-label, randomized, single-center, two-period, two-sequence crossover study involved 24 healthy female volunteers who received single subcutaneous doses of both formulations, separated by a 10-day washout period. Participants underwent pituitary down-regulation using Diphereline^® to minimize endogenous FSH levels. Pharmacokinetic parameters, including peak concentration (C_max), area under the drug-time curve from 0 to t (AUC_0-t), and AUC from 0 to infinity (AUC_0-∞) were measured, and bioequivalence was assessed based on the 90% confidence intervals (CIs) falling within the 80.00-125.00% range. Safety and immunogenicity were also evaluated.</p><p><strong>Results: </strong>The geometric mean ratios (GMRs) and 90% CIs for baseline-corrected AUC_0-t, AUC_0-∞, and C_max of the test formulation relative to the reference formulation were 99.99% (93.57-106.86), 102.70% (93.31-113.03), and 93.41% (87.77-99.41), respectively; all within the predefined bioequivalence range. Safety profiles were similar between the two formulations, with no suspected unexpected serious adverse reaction (SUSAR) identified.</p><p><strong>Conclusion: </strong>The novel prefilled rh-FSH injection (GenSci008) is bioequivalent to the reference formulation (Jinfollin^®), offering a user-friendly and precise alternative for subcutaneous administration in the treatment of infertility.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"241-252"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621001","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":"Assessment of Pharmacokinetics and Safety with Bioequivalence of the Nitroglycerin Sublingual Tablets of Two Formulations in Chinese Healthy Subjects: A Bioequivalence Study.","authors":"Qinjiao Fu, Chunqi Huang, Yuan Yuan, Yu Wang, Bin Zhu, Yanzhu Liu, Fang Tian, Xiufeng Xu, Lei Yang, Yingying Xu, Ying Wang","doi":"10.1007/s40268-025-00519-4","DOIUrl":"10.1007/s40268-025-00519-4","url":null,"abstract":"<p><strong>Background and objective: </strong>Nitroglycerin, a cornerstone therapy for acute angina pectoris, achieves rapid symptom relief through sublingual administration by bypassing hepatic first-pass metabolism. This study aimed to investigate the pharmacokinetics (PK), bioequivalence, and safety profiles between a test (T) formulation and a reference (R) formulation of nitroglycerin sublingual tablets in healthy volunteers (HVs).</p><p><strong>Methods: </strong>In this single-center, randomized, open, single-dose, two-part formulations, four-cycle, two-sequence complete repeat crossover design, fasting-dose bioequivalence study, HVs (n = 36) were 1:1 divided into two groups (T-R-T-R and R-T-R-T) and received 0.6 mg of nitroglycerin sublingual with a 3 d washout. Venous blood was collected 3 h after each administration. Plasma levels of nitroglycerin were analyzed using a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) technique, and PK parameters were calculated using noncompartmental methods.</p><p><strong>Results: </strong>For nitroglycerin, the bioequivalence between the test and reference formulations was assessed using the Reference-Scaled Average Bioequivalence (RSABE) method for the maximum plasma concentration (C_max), area under the curve (AUC) from t = 0 to infinity (AUC_0-∞) and AUC from t = 0 to the final measurable concentration (AUC_0-t). Results showed that the least squares geometric mean ratios (T/R) of C_max, AUC_0-t, and AUC_0-∞ for nitroglycerin (94.62%, 89.92%, and 89.44%, respectively) were in the range of 80.00-125.00%, and the upper limit of unilateral 95% confidence interval (CI) of C_max, AUC_0-t, and AUC_0-∞ for nitroglycerin (-0.06, -0.03, and -0.03, respectively) were less than 0. Safety profiles were comparable between formulations, with no serious adverse events (AE) reported.</p><p><strong>Conclusions: </strong>The study confirmed bioequivalence between the test and reference formulations, demonstrating equivalent absorption rates (C_max) and extents (AUC). Rapid therapeutic plasma levels were achieved via sublingual administration, aligning with nitroglycerin's clinical need for prompt angina relief. These findings, combined with favorable safety data, support the test formulation as a therapeutically equivalent alternative.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"263-274"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144805089","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":"Systematic Review and Meta-analysis of the Clinical Efficacy of Octreotide in Combination with Ulinastatin in the Treatment of Acute Pancreatitis.","authors":"Long-Xun Zhu, Yong Chen, Xiang-Fan Chen, Nan Sheng, Pan-Feng Feng","doi":"10.1007/s40268-025-00518-5","DOIUrl":"10.1007/s40268-025-00518-5","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objectives: &lt;/strong&gt;Acute pancreatitis (AP) is a serious disease characterized by local inflammatory responses in the pancreas. The annual incidence rate of acute pancreatitis is 4.9-73.4 per 100,000 people. Among these, approximately 20% develop into moderately severe acute pancreatitis (MSAP) or severe acute pancreatitis (SAP), with a mortality rate of 13-35%. The aim of this study is to evaluate the efficacy and safety of octreotide in combination with ulinastatin in the treatment of acute pancreatitis using meta-analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Chinese and English databases, including China National Knowledge Infrastructure Database (CNKI), WanFang database (WANFANG), Chinese Scientific Journals Full-text Database (VIP database), PubMed, Medline, and Web of Science, were searched for randomized controlled trials (RCTs) about octreotide in combination with ulinastatin in the treatment of acute pancreatitis from January 2019 to April 2024. Retrieved literature was screened independently by two researchers, and the methodological quality of included publications was evaluated according to bias risk assessment tool recommended by Cochrane 5.1. Data were statistically analyzed by using RevMan5.3 software.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 3026 patients from 30 studies in accordance with the criteria were included, including experimental group (n = 1516) and control group (n = 1510). Meta-analysis results showed that octreotide combined with ulinastatin could increase the effective rate of treatment for acute pancreatitis (relative risk (RR) = 1.23, 95% CI 1.19-1.27, P &lt; 0.00001). The time in the experimental group for hospitalization (standardized mean difference (SMD) = -2.00, 95% CI [-2.67, -1.34], P &lt; 0.00001), disappearance of abdominal pain (SMD = -1.75, 95% CI [-2.21, -1.29], P &lt; 0.00001), disappearance of nausea and vomiting (SMD = -2.03, 95% CI [-2.93, -1.13], P &lt; 0.00001), disappearance of abdominal distension (SMD = -2.02, 95% CI [-2.59, -1.44], P &lt; 0.00001), and disappearance of peritoneal irritation (SMD = -2.20, 95%CI [-3.95, -0.46], P &lt; 0.00001) was shorter than in the control group. The levels in the experimental group of TNFα (SMD = -2.01, 95% CI [-2.71, -1.32], P &lt; 0.00001), CRP (SMD = -2.50, 95% CI [-3.20, -1.79], P &lt; 0.00001), IL-6 (SMD = -2.67, 95% CI [-3.48, -1.85], P &lt; 0.00001), IL-8 (SMD = -2.92, 95% CI [-4.02, -1.83], P &lt; 0.00001), serum amylase concentration (SMD = -2.83, 95% CI [-4.07, -1.60], P &lt; 0.00001), and urine amylase concentration (SMD = -2.34, 95% CI [-3.81, -0.88], P &lt; 0.00001) were lower compared with control group. There was no statistically significant difference in the incidence of adverse reactions between the experimental and control groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The combination of octreotide and ulinastatin can improve the intestinal mucosal barrier function, reduce inflammatory response, and decrease amylase levels in patients with acute pancreat","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"195-207"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334258","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}