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":"https://doi.org/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":""},"PeriodicalIF":2.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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}

{"title":"Pharmacokinetic Comparison of Novel Tablet-in-Tablet and Conventional Ketorolac Tromethamine Tablets in Beagle Dogs.","authors":"Xiang-Yang Xie, Yuan Zeng, Zhi-Long Chen, Yu-Liang Li, Wen Lin, Hui Liu, Yi-Hui Ma, Guo-Wei Zhang","doi":"10.1007/s40268-025-00516-7","DOIUrl":"10.1007/s40268-025-00516-7","url":null,"abstract":"<p><strong>Background and objective: </strong>Ketorolac tromethamine (KT), a nonsteroidal anti-inflammatory drug (NSAID) and cyclooxygenase inhibitor, is commonly used for the management of moderate to severe pain. The objective of this study was to compare the pharmacokinetic characteristics of KT in beagle dogs following oral administration of conventional tablets and a novel tablet-in-tablet (TIT) formulation.</p><p><strong>Methods: </strong>A comparative dissolution study was conducted to evaluate the release profiles of both formulations. Non-compartmental analysis was used to determine the pharmacokinetic parameters of each formulation.</p><p><strong>Results: </strong>Approximately 20% of the administered KT from the TIT formulation was released within the first 30 min, with a cumulative release exceeding 90% at 16 h. In contrast, the conventional tablets released about 50% of the drug within 30 min and completed the release at 4 h. In the single-dose study, the time to reach maximum plasma concentration (T_max) for conventional tablets was 1 h, while T_max for the TIT formulation was 5 h. Both maximum concentration (C_max) and area under the concentration-time curve (AUC) for the TIT formulation were lower than those for conventional tablets. In the repeated-dose study, when equivalent doses (35 mg) of conventional tablets were administered in divided daily doses, the TIT formulation showed no significant differences in most steady-state pharmacokinetic parameters, except for T_max,ss.</p><p><strong>Conclusion: </strong>The results of this study suggest that the development of a novel KT tablet formulation utilizing the push-pull osmotic pump (PPOP) and tablet-in-tablet techniques warrants further investigation in clinical trials.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"209-219"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340550","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":"Demonstrating Bioequivalence for a Lumacaftor Monosubstance Formulation Versus Orkambi^® (Lumacaftor/Ivacaftor) in Healthy Subjects.","authors":"Alexandra Papaelias, Darcy Lidington, Steffen-Sebastian Bolz","doi":"10.1007/s40268-025-00514-9","DOIUrl":"10.1007/s40268-025-00514-9","url":null,"abstract":"<p><strong>Background and objective: </strong>Lumacaftor is an active ingredient in the US Food and Drug Administration-approved combination medication Orkambi^®, which is used for treating cystic fibrosis. Experimental evidence suggests that lumacaftor can be used as a monotherapy to improve brain perfusion and memory in heart failure. To clinically assess this therapeutic intervention, a formulation with demonstrated bioequivalence to the currently approved combination product is required.</p><p><strong>Methods: </strong>This comparative bioavailability and food-effect study compared lumacaftor pharmacokinetics in healthy patients following: (i) oral administration of lumacaftor (400 mg; Test Product) or Orkambi^® (lumacaftor 400 mg/ivacaftor 250 mg; Reference Product) in the fed state and (ii) oral administration of lumacaftor (400 mg; Test Product) in the fasted to fed state. Plasma lumacaftor concentrations were measured with a standard liquid chromatography with tandem mass spectrometry approach.</p><p><strong>Results: </strong>The \"Test-to-Reference ratio\" of the geometric least-square means for maximum plasma concentration and area under the curve met the Food and Drug Administration-defined criteria for bioequivalence; median times to maximum plasma concentration values were not statistically different. The \"Fed to Fasted ratio\" of the geometric least-square means for maximum plasma concentration and area under the curve indicated a clear food effect on bioavailability. Lumacaftor exposure was approximately two times higher when administered with fatty foods than when taken in a fasting state. The monosubstance formulation was well tolerated.</p><p><strong>Conclusions: </strong>We conclude that the lumacaftor monosubstance formulation delivers lumacaftor exposure that is not meaningfully different than the currently approved combination product.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov identifier: NCT05968612.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"221-229"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477586","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":"Drugs for Procedural Sedation and Analgesia in Children: A Systematic Review and Meta-analysis.","authors":"Sandrella Hamdan, Samuel Adelou, Sébastien Jungo, Hadrien Diakonoff, Jean-Marc Treluyer, Hélène Fron Chabouis, Violaine Smail-Faugeron","doi":"10.1007/s40268-025-00522-9","DOIUrl":"10.1007/s40268-025-00522-9","url":null,"abstract":"<p><strong>Background and objectives: </strong>Performing medical procedures on children can often be challenging because of the anxiety that these procedures may induce, the need for immobility that they may require, or age-related development capabilities. We assessed the effects of procedural sedation and analgesia drugs for anxiety management in children during medical procedures.</p><p><strong>Methods: </strong>We searched PubMed Medline, Cochrane Library, American Academy of Pediatrics, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, and references of eligible studies. We included parallel-arm randomized controlled trials comparing different active drugs of procedural sedation and analgesia in children undergoing diagnostic or therapeutic, painful or nonpainful procedures. Two authors independently screened titles/abstracts, reviewed full-texts, and extracted data related to study characteristics, methodology, participants, and results. Meta-analyses involved the Mantel-Haenszel random-effects approach.</p><p><strong>Results: </strong>We included 98 studies (9161 children) in the qualitative analysis and 50 in the quantitative analysis. The probability of successful sedation rate was associated with dexmedetomidine versus midazolam alone (odds ratio [OR] 7.42, 95% confidence interval [CI] 4.08-13.48) and with midazolam and ketamine combined versus midazolam alone (OR 3.0, 95% CI 1.67-5.39). The probability of successful sedation rate was associated with dexmedetomidine 2 μg/kg versus 1 μg/kg (OR 5.21, 95% CI 1.90-14.27).</p><p><strong>Conclusions: </strong>Dexmedetomidine, and the combination of midazolam and ketamine, seem interesting for sedating children during medical procedures.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"179-193"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849380","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":"In-Vitro Comparison of Physical Characteristics, Enzyme Content, and Release Kinetics of Pancreatic Enzyme Preparations Available in Europe and Canada.","authors":"Sven Hartmann, Jonas Rosendahl, Amy Todd, Emma Bennett-Huntley, J Enrique Domínguez-Muñoz","doi":"10.1007/s40268-025-00515-8","DOIUrl":"10.1007/s40268-025-00515-8","url":null,"abstract":"<p><strong>Introduction: </strong>Commercially available pancreatic enzyme replacement therapy (PERT) preparations differ significantly in their physical and enzyme properties, raising concern about the interchangeability of these preparations. The current study aimed to compare various commercially available PERT in Europe and Canada for physical properties, enzyme content, enzyme activities, release characteristics, and compliance with the label claim.</p><p><strong>Methods: </strong>Particle size was determined using a dynamic image analyzer and represented as Feret Max at 10th (FERET Max D [v, 0.1]), 50th (FERET Max D [v, 0.5]), and 90th percentiles (FERET Max D [v, 0.9]). Particle imaging was performed using scanning electron microscopy and a Quorum sputter coater. Lipase activity was measured according to the European Pharmacopoeia (Ph. Eur) and International Pharmaceutical Federation (FIP) procedures. The measured activity was compared against the label claims to identify the percentage of deviations. Lipase release at different pH (release kinetics) was also determined subsequently.</p><p><strong>Results: </strong>The particle size of the PERT preparations differed considerably. There were deviations in the actual lipase content from the label claim, ranging from 85.8% (Gastrozym 10000) to 177.5% (Pancreolan 6000). Under the simulated conditions, most PERT preparations released the enzyme lipase at an acidic pH present in the stomach before reaching the duodenum.</p><p><strong>Conclusion: </strong>PERT preparations available in Europe and Canada exhibit significant differences in terms of physical and enzyme release kinetics. Careful evaluation is needed when interchanging these preparations, as it could impact the therapeutic outcomes.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"231-240"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144498969","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}