Drugs in Research & Development最新文献

{"title":"Biochemical Characterization and Stability of a New Fibrinogen Concentrate (BT524) Manufactured Using an Innovative Virus Inactivation Step.","authors":"Linda Schulte, Boris Fürtig, Christoph Scheich, Steffen Kistner, Maja Klaus, Jonas Benjamin Michaelis, Florian Sochor, Oliver Maneg","doi":"10.1007/s40268-026-00550-z","DOIUrl":"https://doi.org/10.1007/s40268-026-00550-z","url":null,"abstract":"<p><strong>Background and objectives: </strong>Human plasma is utilized in the production of life-saving pharmaceuticals, including fibrinogen, a key player in clot formation, tissue repair, and hemostasis. Fibrinogen deficiency results in impaired blood clotting and potentially severe hemorrhagic events. Fibrinogen concentrate or cryoprecipitate are the preferred options for fibrinogen replacement therapy. Both increase plasma fibrinogen levels, but utilization of fibrinogen concentrate is advantageous. It offers enhanced pathogen safety through manufacturing procedures that remove or inactivate viruses or prions potentially present in human plasma.</p><p><strong>Method: </strong>We developed a novel manufacturing process that yields a fibrinogen concentrate (BT524) and coagulation factor VIII (Haemoctin^® SDH) in one workflow. This process contains several virus inactivation steps, including an innovative UV-C irradiation and a cation exchange chromatography (CEX) step for prion removal.</p><p><strong>Results: </strong>While successfully inactivating potential viral contamination, UV-C irradiation showed no influence on fibrinogen structure and composition, and no formation of neoantigenic structures could be identified. Fibrinogen concentrate (BT524) contained almost exclusively fibrinogen with activity close to 100%, very low numbers of sub-visible particles and lacked measurable thrombogenic activity. The stability study of clinical material demonstrated a stable product for five years under several storage conditions. With a solubility at room temperature of 2-4 min upon reconstitution using the nextaro^®v transfer device, the fibrinogen concentrate is almost immediately ready to use. The reconstituted solution demonstrated physico-chemical stability for 24 h.</p><p><strong>Conclusion: </strong>Fibrinogen concentrate (BT524) generated using the novel manufacturing process yielded a product of high quality, purity and virus safety. In addition, it offers excellent solubility, long-term stability and high activity. The integration of shared process steps with Haemoctin^® SDH facilitates a more ethical and efficient utilization of human blood plasma. In clinical trials, the potency, safety and tolerability of the manufactured fibrinogen concentrate were demonstrated.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149276241","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":"Population Pharmacokinetics of Intravenous and Subcutaneous Belimumab, and Clinical Response Prediction in Chinese Pediatric Patients with Systemic Lupus Erythematosus.","authors":"Junyi Wu, Richard Dimelow, Scott Marshall, Xuan Zhou","doi":"10.1007/s40268-026-00549-6","DOIUrl":"https://doi.org/10.1007/s40268-026-00549-6","url":null,"abstract":"<p><strong>Background and objective: </strong>Intravenous (IV) and subcutaneous (SC) belimumab are approved in the USA, Europe, and Japan for patients aged ≥ 5 years with active systemic lupus erythematosus. In China, IV belimumab is approved for patients aged ≥ 5 years. This analysis updates the global pediatric population pharmacokinetic model by integrating data from IV and SC Chinese pediatric studies and evaluates the suitability of a 200-mg SC dosing regimen for pediatric systemic lupus erythematosus in China.</p><p><strong>Methods: </strong>This analysis utilized the previously established two-compartment model while re-evaluating the impact of potential covariates. Allometric scaling was incorporated to account for variations in body size, and other covariates were systematically assessed through stepwise selection and their relevance to pharmacokinetic parameters. To support extrapolation of the established efficacy from the IV belimumab pediatric study to SC belimumab in pediatric patients, simulations were conducted to compare pharmacokinetic exposures between the proposed SC and approved IV regimens in Chinese pediatric patients. Furthermore, to provide additional evidence for supporting dose selection in this population, clinical response was predicted using a pre-established exposure-response model.</p><p><strong>Results: </strong>The estimated pharmacokinetic parameters for a representative Chinese pediatric patient were: clearance, 158 mL/day; steady-state volume of distribution, 3930 mL; SC bioavailability, 77.9%. Identified significant covariates included body weight (influencing clearance and volume of distribution), and baseline immunoglobulin G and albumin levels (affecting clearance). A systematic bias of -34% in drug concentrations was observed in Chinese versus global studies. This discrepancy is unlikely to stem from racial or physiological differences and may instead be attributed to study operational factors. The established exposure-response model confirmed that simulated exposures for IV and SC regimens in Chinese pediatric patients reached the plateau of the exposure-response curve. Further simulations demonstrated that both the two-weight-band SC regimen and the trial-studied three-weight-band regimen produced exposures comparable to the IV regimen in Chinese pediatric patients.</p><p><strong>Conclusions: </strong>This analysis supports the suitability of a two-weight-band, dosing interval-adjusted 200-mg SC regimen for Chinese pediatric patients with systemic lupus erythematosus. Compared with the three-weight-band regimen, the two-weight-band approach simplifies administration and enhances feasibility for clinical implementation.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246905","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":"Analytical Characterization for Similarity Assessment Between Biosimilar SB16 and Denosumab Reference Product Using State-of-the-Art Analytical Method.","authors":"Eunok Jung, Jinyoung Kim, Misol Do, Jihye Kim, Hanseul Kweon, Jaeil Lee, Jungmin Lee, Taekyung Yoo, Sung-Yong Yang","doi":"10.1007/s40268-026-00555-8","DOIUrl":"https://doi.org/10.1007/s40268-026-00555-8","url":null,"abstract":"<p><strong>Background and objective: </strong>SB16 has been developed and recently approved as a biosimilar to denosumab reference product, which inhibits osteoclast formation by targeting receptor activator of nuclear factor kappa-B ligand. This study presents a comprehensive analytical characterization of SB16 denosumab biosimilar to demonstrate high similarity to the reference product (Prolia and Xgeva).</p><p><strong>Methods: </strong>Analytical similarity was assessed using side-by-side comparisons and similarity range approaches with state-of-the-art methods. Critical quality attributes evaluated included primary structure, post-translational modifications, higher order structure, purity, glycosylation, charge heterogeneity, and biological activities. Similarity ranges were established using extensive reference product lot testing (up to 68 EU Prolia, 35 US Prolia, 29 EU Xgeva, and 17 US Xgeva lots).</p><p><strong>Results: </strong>Peptide mapping confirmed 100% sequence coverage with identical amino acid sequences. Higher order structure analyses (circular dichroism, Fourier transform infrared, differential scanning calorimetry, hydrogen/deuterium exchange-mass spectrometry) demonstrated similar secondary and tertiary structures. Purity assessments (size exclusion-high performance liquid chromatography, Capillary electrophoresis-sodium dodecyl sulfate) showed similar monomer content and impurity profiles. N-glycan profiling revealed similar high mannose species; galactosylation differences were deemed not clinically meaningful. Charge heterogeneity (imaging capillary isoelectric focusing, cation exchange) demonstrated similar charge variant profiles. Fab-related activities (receptor activator of nuclear factor kappa-B ligand binding, receptor activator of nuclear factor kappa-B ligand neutralization, and anti-differentiation) and Fc-related activities (neonatal fragment crystallizable receptor binding, Fc-gamma receptor binding, C1q binding, antibody-dependent cell-mediated cytotoxicity, and complement-dependent cytotoxicity) showed similar results.</p><p><strong>Conclusions: </strong>SB16 demonstrated high similarity to denosumab reference product across all structural, physicochemical, and biological properties, providing robust analytical evidence supporting biosimilarity. This dataset serves as valuable reference information for biosimilar development.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149247075","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":"Anti-Fungal and Toxicology Assessment of ISFP10, an Inhibitor of Fungal Phosphoglucomutase (PGM).","authors":"Madeline R Pellegrino, Marc Bindzus, Theodore J Kottom, Savita Ayyalasomayajula, Conrad C Achilonu, Eunhee S Yi, Andrew H Limper","doi":"10.1007/s40268-026-00551-y","DOIUrl":"10.1007/s40268-026-00551-y","url":null,"abstract":"<p><strong>Background and objective: </strong>The novel small molecule ISFP10 inhibits fungal phosphoglucomutase (PGM) activity in Aspergillus fumigatus and Pneumocystis spp. With 50-fold selectivity over the human isoform, conferred by a conserved cysteine residue present in several pathogenic fungi, ISFP10 may represent a promising broad-spectrum antifungal. We evaluated its activity against Candida albicans and Candida glabrata, followed by toxicology assessment in mice.</p><p><strong>Methods: </strong>Minimum inhibitory concentration susceptibilities were performed on three strains of C. albicans and C. glabrata and compared with fluconazole. Growth inhibition was further assessed in an 8-h, concentration-dependent growth assay. For toxicology, C57BL6 mice received once-daily intraperitoneal injections of vehicle control (dimethyl sulfoxide) or ISFP10 (10 mg/kg) for 7 days. Body weight, complete blood count (CBC), blood chemistry, histopathology of major organs, and lung extracellular matrix (ECM) and cytokine levels (ELISA, qPCR) were analyzed.</p><p><strong>Results: </strong>ISFP10 inhibited all tested Candida strains with significantly greater potency than fluconazole. It also showed concentration-dependent inhibition of growth in liquid culture. In mice, no significant differences in daily or final body weight, ECM transcript levels, or interleukin (IL)-6 expression were observed between groups. Tumor necrosis factor-α (TNFα) levels in lung tissue were significantly reduced in ISFP10-treated animals, suggesting a potential anti-inflammatory effect. Blood chemistry and CBC revealed minor abnormalities (increased neutrophils, decreased potassium), but these were not clinically significant. Histopathologic evaluation showed no evidence of organ toxicity.</p><p><strong>Conclusions: </strong>ISFP10 demonstrates potent antifungal properties against C. albicans and C. glabrata and a favorable safety profile in vivo, supporting its further development as a potential broad-spectrum antifungal agent.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149065490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the Pharmacokinetics and Pharmacodynamics of Transdermal Estradiol Gel Administered Repeatedly in Postmenopausal Women.","authors":"Jouni Sirviö, Tuula Ahtola-Sätilä, Merja Kirjavainen, Paula Rytilä","doi":"10.1007/s40268-026-00552-x","DOIUrl":"https://doi.org/10.1007/s40268-026-00552-x","url":null,"abstract":"<p><strong>Background and objective: </strong>Transdermal administration of estrogen has established its positioning among hormone replacement therapies in menopause. In Divigel® (estradiol hemihydrate gel 0.1%), 17β-estradiol, a body-identical estrogen, is formulated to be absorbed through the skin. This study aimed to provide systematic data on the pharmacokinetics and pharmacodynamics of Divigel to further enable its use in individualized therapies.</p><p><strong>Methods: </strong>The study was conducted over a 14-day treatment period using three escalating doses (0.5 mg, 1.0 mg, and 1.5 mg) in ten postmenopausal women. A 3-day or 4-day follow-up period was conducted after each treatment period. Wash-out between the periods was at least 2 weeks. The serum levels of estradiol (E2) and its metabolite estrone (E1) were analyzed, and the therapeutically informative ratio of E2/E1 was calculated. In addition, the temporal course of the excretion of E1, E2, and estriol (E3) in urine was studied. Serum levels of gonadotropins, follicle-stimulating hormone and luteinizing hormone, were measured as pharmacodynamic biomarkers.</p><p><strong>Results: </strong>Serum concentrations of E2 were proportional to dose, and profiles were dose dependent. A steady-state E2 concentration was achieved within 3-5 days of daily administration of 1.0-mg and 1.5-mg doses. After the first and last application, the serum E2/E1 ratio increased clearly above 1.0 within 2-12 hours post-dose, i.e., approximating premenopausal levels, whereas it returned and remained close to parity at steady state, which still is clearly above the measured baseline (menopausal) levels. The urine levels of E1 and E3 were comparable and much higher than E2 urine levels. After the last application on day 14, the average serum concentration values of E2 (calculated as area under the concentration-time curve from time 0 to 24 hours divided by the 24-hour application interval) were 12.4 ± 7.0, 29.7 ± 7.3, and 55.0 ± 33.1 pg/mL at 0.5-mg, 1.0-mg and 1.5-mg doses, respectively. Those fit into the clinically effective concentration range at the doses of 1.0 mg or 1.5 mg in all the subjects. Follicle-stimulating hormone levels were lower after application of Divigel at every dose compared with their pre-dosing baseline. Luteinizing hormone levels also decreased following E2 administration. Treatment was well tolerated, and no safety concerns or skin reactions were observed.</p><p><strong>Conclusions: </strong>Transdermal estradiol treatment with Divigel produced dose-proportional, clinically meaningful serum E2 levels and E2/E1 ratios in postmenopausal women. All administered doses also showed expected hormonal pharmacodynamic effects and were well tolerated.</p><p><strong>Clinical trial registration: </strong>Not applicable in the USA and European Union for a pharmacokinetic study commenced in 1999.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148921609","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":"Comparative Pharmacokinetics of Trientine Dihydrochloride Capsules: A Randomized, Open-Label, Reference-Controlled, Two-Period Crossover Study in Healthy Volunteers.","authors":"Christian J Hartmann, Frank Tacke, Isabelle Mohr, Michael Praktiknjo, Martin Jankofsky, Steffen Wahler, Karl Heinz Weiss","doi":"10.1007/s40268-026-00553-w","DOIUrl":"https://doi.org/10.1007/s40268-026-00553-w","url":null,"abstract":"<p><strong>Background and objectives: </strong>Trientine dihydrochloride (TETA-2HCl) is an oral copper chelator used for Wilson disease. Because available formulations differ in marketed strength and may have formulation-specific pharmacokinetic properties, this study compared a 250 mg test capsule and a 300 mg reference capsule administered under fasting conditions.</p><p><strong>Methods: </strong>This randomized, open-label, balanced, two-treatment, two-period, two-sequence crossover study enrolled 36 healthy adults. Plasma samples collected over 48 h after single-dose administration were analyzed for parent trientine and N1-acetyltriethylenetetramine using validated liquid chromatography (LC)-tandem mass spectrometry (MS/MS). The primary comparative pharmacokinetic evaluation was based on parent trientine C_max and AUC_0-t at the administered strengths. Dose-normalized and metabolite analyses were supportive.</p><p><strong>Results: </strong>Thirty-five participants were included in the pharmacokinetic and statistical analyses. Parent trientine was absorbed more rapidly after the test formulation, with median T_max values of 1.25 versus 2.25 h. At the administered strengths, test/reference geometric least-squares mean ratios (90% confidence intervals) were 114.96% (104.40-126.60) for C_max and 109.36% (98.40-121.55) for AUC_0-t. Dose-normalized ratios were 137.95% (125.28-151.92) and 131.24% (118.08-145.86), respectively, indicating higher exposure per milligram for the test formulation. Metabolite findings were supportive and did not determine the primary comparative conclusion. No serious adverse events occurred; five mild adverse events were reported during post-study safety assessment.</p><p><strong>Conclusions: </strong>At the administered strengths, AUC_0-t was similar between the formulations, whereas the upper confidence limit for C_max slightly exceeded 125.00%. Faster absorption and higher dose-normalized exposure with the test formulation indicate formulation-dependent pharmacokinetic differences and support cautious use of bioequivalence terminology outside the specific regulatory assessment context.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148921605","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":"Optimizing Drug-Resistant Epilepsy Management: Cenobamate's role in the Surgery/Neuromodulation Pathway.","authors":"Giancarlo Di Gennaro, Paolo Bonanni, Francesco Deleo, Antonio Gambardella, Roberto Michelucci, Giada Pauletto, Nicola Specchio, Alfredo D'Aniello","doi":"10.1007/s40268-026-00548-7","DOIUrl":"10.1007/s40268-026-00548-7","url":null,"abstract":"","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"197-201"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148551020","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":"Ustekinumab in the Management of Perianal Fistulizing Crohn's Disease: Current Evidence and Practical Strategies.","authors":"Bolin Yang","doi":"10.1007/s40268-026-00545-w","DOIUrl":"10.1007/s40268-026-00545-w","url":null,"abstract":"<p><p>Perianal fistulizing Crohn's disease (PFCD) is a severe and complex manifestation associated with high morbidity and limited treatment durability. Ustekinumab is a monoclonal antibody targeting the interleukin-12/23 pathway, which is involved in the pathogenesis of PFCD. Evidence from post hoc analyses and real-world studies has shown the therapeutic potential of ustekinumab in both anti-tumor necrosis factor-experienced and selected biologic-naïve patients with PFCD. Preliminary evidence has indicated that the treatment effect may be improved when used in combination with surgical interventions such as seton placement or sphincter-preserving procedures. Adjunctive antibiotics during induction and early monitoring of clinical and radiologic response may further enhance outcomes. While ustekinumab is increasingly being incorporated into multidisciplinary PFCD management, prospective fistula-specific trials are needed to clarify its optimal positioning. Future research should also focus on predictive biomarkers and treatment algorithms to support personalized and durable care.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"141-153"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147989717","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 Combination of the Tryptophan Hydroxylase Inhibitor Telotristat with the mTOR Inhibitor Everolimus as an Effective Strategy Against Neuroendocrine Tumors.","authors":"Javier Molina-Cerrillo, Arantzazu Sierra-Ramirez, José L López-Aceituno, Marinela Méndez-Pertuz, Teresa Alonso-Gordoa, Michael Linnebacher, Matteo Santoni, Pablo J Fernandez-Marcos, Enrique Grande","doi":"10.1007/s40268-026-00544-x","DOIUrl":"10.1007/s40268-026-00544-x","url":null,"abstract":"<p><strong>Background and objectives: </strong>Neuroendocrine tumors are a rare and heterogeneous group of neoplasms that frequently cause carcinoid syndrome, characterized by diarrhea, flushing, and carcinoid heart disease. A recent therapy for carcinoid syndrome involves inhibition of tryptophan hydroxylase, the rate-limiting enzyme in serotonin synthesis, using telotristat ethyl. Telotristat has demonstrated clinical control of carcinoid syndrome; however, its potential antitumoral effects remain unclear. This study aimed to evaluate the antitumor activity of telotristat ethyl alone and in combination with everolimus in neuroendocrine tumor models.</p><p><strong>Methods: </strong>Cell viability was assessed in three neuroendocrine tumor cell lines of pancreatic (BON-1, QGP-1) and intestinal (HROC57) origin following treatment with telotristat ethyl. Combination treatments with telotristat ethyl and everolimus or other antitumoral agents were evaluated for effects on cell viability, apoptosis, and cell cycle distribution. In vivo efficacy was examined in nude mice bearing BON-1-derived xenografts treated with telotristat ethyl, everolimus, or the combination. Tumor growth, toxicity, proliferation (Ki67), and apoptosis (active caspase-3) were analyzed.</p><p><strong>Results: </strong>Telotristat ethyl reduced cell viability in all three neuroendocrine tumor cell lines. Combination with everolimus, but not with other antitumoral treatments, synergistically decreased cell viability, induced apoptosis, and reduced the proportion of cells in the G2/M phase. In nude mice bearing BON-1 xenografts, combined treatment with telotristat ethyl and everolimus arrested tumor growth without signs of toxicity compared with single treatments. At the end of treatment, tumors from combination-treated mice showed a reduction in proliferation (Ki67) comparable to single-treated groups and an increase in apoptosis as indicated by active caspase-3.</p><p><strong>Conclusions: </strong>Telotristat ethyl exhibits antitumoral activity in neuroendocrine tumor models in vivo. Moreover, the combination of telotristat ethyl and everolimus, two therapies already used in clinical practice, may represent a safe and effective therapeutic strategy for neuroendocrine tumors.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"155-167"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148007264","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":"Gabapentin Extended Release Tablets in Healthy Subjects Under Fed Conditions: A Randomized, Open-Label, Two-Treatment, Two-Period, Two-Sequence, Single Dose, Crossover, Comparative Bioavailability Study.","authors":"Sudershan Kumar, Arshad Khuroo, Sanjay Jagannath Gurule, Sachin Mehra, Hari Krishan Tiwari, Y Zala, Venkata Rama Rao Kamala, Madhu Kandukuri, Shruti Dharmadhikari, Prashant Devkare, Chintan Khandhedia","doi":"10.1007/s40268-026-00547-8","DOIUrl":"10.1007/s40268-026-00547-8","url":null,"abstract":"<p><strong>Background: </strong>Gabapentin is effective for treating post-herpetic neuralgia and neuropathic pain by stabilizing nerve activity through blocking calcium channels and reducing neurotransmitter release. Gabapentin is available in immediate-release (IR) and extended-release (ER) formulations. A comparative bioavailability study was conducted between Gabapentin ER 600 mg tablets once-daily (OD) (Gabantin^® GRS) [Test (T)] (manufactured by Sun Pharmaceuticals Industries Limited), and Gabapentin Tablets 600 mg OD (Gralise^®) [Reference (R)] (distributed by Almatica Pharma LLC) in healthy human male adults under fed conditions.</p><p><strong>Methods: </strong>In this open-label, balanced, randomized, crossover study each subject received a 600 mg single dose of either T or R in Period 1, followed by crossover treatment in Period 2, with a washout period of 12 days in-between. Pharmacokinetic parameters, including C_max, AUC_0-t, and AUC_0₋∞, were assessed. Safety was monitored through treatment-emergent adverse events (AEs).</p><p><strong>Results: </strong>All 24 enrolled subjects completed the study. The test formulation demonstrated comparable pharmacokinetic profile to the reference product, meeting the criteria for bioequivalence within acceptable limits (0.80-1.25). The percentage ratio for T vs R product was 0.9171 (90% confidence interval [CI] 0.826-1.0183) for AUC_0-t, 0.9191 (90%CI 0.8279-1.0203) for AUC_0-∞ and 0.9135 (90%CI 0.8324-1.0026) for C_max. Plasma concentration-time profiles were similar. One AE of fever was reported after administration of T; no serious adverse event was reported.</p><p><strong>Conclusions: </strong>Gabantin^® GRS 600 Tablet ER OD of Sun Pharma had a similar pharmacokinetic profile and was bioequivalent to Gralise^® in healthy subjects under fed conditions with good safety and tolerability profiles.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"187-196"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148370638","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}