Pharmacology Research & Perspectives最新文献

{"title":"Morphological and Biochemical Insights Into the Renoprotective Effects of Combined N-Acetylcysteine and Glycine Treatment in Experimental Diabetic Nephropathy.","authors":"Malik Ejubović, Andrej Belančić, Yun Wah Lam, Farideh Javid, Dina Kapić, Esad Ćosović, Rijad Jahić, Orhan Lepara, Amira Jagodić Ejubović, Lejla Alić, Amil Topuz, Zurifa Ajanović, Almir Fajkić","doi":"10.1002/prp2.70273","DOIUrl":"10.1002/prp2.70273","url":null,"abstract":"<p><p>Diabetic nephropathy (DN) is a major microvascular complication of diabetes mellitus and the leading cause of end-stage renal disease. Oxidative stress and inflammation are central drivers of DN progression, yet no effective therapies exist to prevent or delay renal injury. This study investigated the renoprotective effects of glycine (GLY), N-acetylcysteine (NAC), and their combination administered at early versus late stages of streptozotocin induced diabetes. Forty-eight male Wistar rats (n = 48) were allocated into five groups: healthy controls (Group 1, n = 6), untreated diabetic rats (Group 2, n = 6), and three treatment groups (Groups 3-5, each n = 12). Diabetes was induced by a single intraperitoneal streptozotocin injection (55 mg/kg). Group 3 received NAC (100 mg/kg), Group 4 received GLY (250 mg/kg), and Group 5 received NAC + GLY. Each treatment group was subdivided into early (6 week, n = 6) and late (12 week, n = 6) intervention subgroups. Treatments were administered orally. Renal tissue was evaluated using classic histology, geometric morphometric analysis, and biochemical assays of superoxide dismutase (SOD) and myeloperoxidase (MPO). Statistical analyzes were performed using ANOVA with appropriate post hoc tests (p < 0.05). Untreated diabetic rats (Group 2) showed significantly decreased SOD activity, increased MPO levels, marked mesangial matrix expansion, glomerular hypercellularity, tubular epithelial degeneration, and interstitial inflammation with fibrosis. NAC (Group 3) and GLY (Group 4) each improved oxidative stress markers and partially restored glomerular and tubular morphology, with early treatment subgroups exhibiting more substantial benefit than late subgroups. The combined NAC + GLY therapy (Group 5) demonstrated the strongest renoprotective effect, preserving renal structure and biochemical parameters closest to healthy controls. To conclude, early combined administration of glycine and N-acetylcysteine yields superior protection against diabetes-induced renal injury compared with individual treatments. These findings support the therapeutic potential of antioxidant-amino acid combinations in preventing or delaying diabetic nephropathy.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 3","pages":"e70273"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13239810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148138791","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":"Investigating the Phytochemical Constituents, Anti-Inflammatory, and Neuropharmacological Activities of Podocarpus neriifolius Leaves Through FT-IR, GC-MS, Experimental Studies, Molecular Docking, and Molecular Dynamics Simulations.","authors":"Neamul Hoque, Md Tashrif Rahman Tipu, Md Abul Bashar, Raju Dash, Kutub Uddin Ahamed, Md Liakot Ali, Md Jahirul Islam Mamun, Bakul Akter, Mohammed Kamrul Hossain, Nawreen Monir Proma","doi":"10.1002/prp2.70272","DOIUrl":"10.1002/prp2.70272","url":null,"abstract":"<p><p>Podocarpus neriifolius, a widely distributed medicinal plant in South and Southeast Asia, has traditionally been used to treat rheumatism and joint pain. This study aimed to investigate the phytochemical profile and therapeutic potential of the ethanolic leaf extract of P. neriifolius (EEPN) using integrated in vitro, in vivo, and in silico approaches. Phytochemical analysis via FT-IR and GC-MS revealed the presence of steroidal glycosides, flavonoids, alkenes, aliphatic compounds, steroids, saponins, and other glycosides. In a COX inhibition assay, EEPN demonstrated notable in vitro anti-inflammatory effects, further validated in a mouse paw edema test. In Swiss albino mice, EEPN (200 and 400 mg/kg) showed increased head dipping in HBT (43.4 ± 1.14 and 69.2 ± 1.22), where the standard showed (57.5 ± 1.01), and improved open-arm entries and time in EPM (260.3 and 280.6 s) compared to the standard (245.2 s). EEPN produced a dose-dependent sedative effect both in HCT and OFT. Furthermore, EEPN significantly lowered immobility time in the tail suspension and forced swimming tests, demonstrating its antidepressant effects. According to molecular docking studies, the phytochemicals in EEPN showed a strong affinity for binding to important drug target proteins linked to inflammation, anxiety, and depression. The EEPN had binding affinities of -6.6, -5.4, and -10 kcal/mol with COX2, GABA_A, and the serotonin transporter, respectively. Protein-ligand complex stability was validated through molecular dynamics simulations analysis. The pharmacokinetic and safety profile of the compounds in ADMET analysis showed druggable qualities within acceptable ranges, implying the possibility as potential medications in the future. However, further research is necessary to ascertain whether P. neriifolius leaves can be utilized as a therapeutic agent.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 3","pages":"e70272"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13238835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148150559","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":"Patterns of Spontaneous Adverse Drug Reaction Reporting in Germany From 2012 to 2021.","authors":"Diana Dubrall, Severin Domgörgen, Patrick Christ, Maike Below, Matthias Schmid, Bernhardt Sachs","doi":"10.1002/prp2.70282","DOIUrl":"10.1002/prp2.70282","url":null,"abstract":"<p><p>The absolute number of spontaneous adverse drug reaction (ADR) reports increased in the past in several national and international ADR databases. However, in most studies drug exposure was not considered. Our study aimed to evaluate the number of ADR reports from Germany in relation to the number of patients with outpatient drug prescriptions stratified by sex, age groups, seriousness, and reporter types (physician versus consumer). Therefore, 407 882 spontaneous ADR reports from Germany, after exclusion of ADR reports related to vaccines, intentional misuses and accidental exposure, submitted between 01.01.2012 and 31.12.2021 were analyzed. The annual numbers of patients with at least one outpatient drug prescription were provided by the Central Research Institute for Ambulatory Health Care in Germany. Reporting rates per year were calculated by dividing the annual number of spontaneous ADR reports by the annual number of patients with at least one outpatient drug prescription. Between 2012 and 2021 (2.4-fold), and strikingly between 2017 and 2018 (2.2-fold), the annual reporting rate increased. This increase appears to be primarily driven by non-serious ADR reports submitted by consumers (32.5-fold increase), whereas reporting rates for serious ADRs and for reports submitted by physicians remained stable. Furthermore, the rise of non-serious ADR reports from consumers was particularly apparent for females aged 12-17 and 18-64 years. Overall, the observed increase of non-serious ADR reports is most likely related to changes in reporting obligations for pharmaceutical companies. Our study suggests that females might report ADRs more frequently.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 3","pages":"e70282"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13260685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148227287","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":"Editorial: Pharmacology Education Special Issue.","authors":"Jennifer A Koenig, Steven J Tucker","doi":"10.1002/prp2.70263","DOIUrl":"10.1002/prp2.70263","url":null,"abstract":"","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 3","pages":"e70263"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856872","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":"Population Pharmacokinetics of the Novel Myeloperoxidase Inhibitor Mitiperstat.","authors":"Mikael Sunnåker, Jacob Leander, Hans Ericsson","doi":"10.1002/prp2.70259","DOIUrl":"10.1002/prp2.70259","url":null,"abstract":"<p><p>Mitiperstat is a novel myeloperoxidase inhibitor being investigated for the treatment of heart failure, metabolic dysfunction-associated steatohepatitis, and chronic obstructive pulmonary disease. Pharmacokinetic data from five clinical trials were used to develop a mitiperstat population pharmacokinetics (popPK) model. In total, 2856 plasma samples from 128 mitiperstat-treated participants were collected during the first-in-human single-ascending dose (SAD) study; multiple-ascending dose studies (MAD) in healthy volunteers, including healthy Japanese and Chinese volunteers (JCMAD); the phase 2a SATELLITE study in patients with heart failure with preserved/mildly reduced ejection fraction (HFpEF/HFmrEF); and from a study in patients with severe renal impairment. The mitiperstat concentration-time data were pooled and analyzed with the software NONMEM. The covariates considered in this analysis were baseline estimated glomerular filtration rate (eGFR), baseline body weight, baseline body mass index, sex, race (Asian or non-Asian), age, disease status (healthy volunteers or patients with HFpEF/HFmrEF), and formulation (oral suspension or tablet). The final popPK model is a two-compartment model with first-order absorption and linear elimination. Baseline body weight, disease status, Asian race, and eGFR were identified as significant covariates for apparent clearance, and age was identified as a significant covariate for apparent central volume of distribution. The final model predicts that severe renal impairment and lower body weight have the largest impact on exposure. Exposure to mitiperstat increased as eGFR declined. This popPK model constitutes an important step toward optimizing doses for efficacy and safety in the different mitiperstat development programs. Trial Registration: ClinicalTrials.gov: NCT02712372.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 3","pages":"e70259"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13154774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841432","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":"The Prophylactic Effect of Dexmedetomidine 0.008% Versus Brimonidine 0.2% on IOP Elevation After Nd: YAG Laser Capsulotomy.","authors":"Parisa Zakeri, Ghodrat Akhavanakbari, Habib Ojaghi, Firouz Amani","doi":"10.1002/prp2.70227","DOIUrl":"10.1002/prp2.70227","url":null,"abstract":"<p><p>Posterior capsule opacification (PCO) is a common post-cataract surgery complication treated with Nd:YAG laser posterior capsulotomy, which may cause intraocular pressure (IOP) spikes and threaten vision. Brimonidine and apraclonidine are widely used to prevent such elevations. This prospective, double-masked, randomized clinical trial evaluated the efficacy of topical dexmedetomidine, a novel ophthalmic drop, in preventing IOP rise after Nd:YAG laser treatment. A total of 111 eyes from 89 pseudophakic patients were randomized to receive dexmedetomidine 0.008% or brimonidine 0.2% one h before the procedure. Patients with glaucoma, baseline IOP > 24 mmHg, keratoconus, corneal edema, prior refractive/corneal surgery, or unstable cardiovascular disease were excluded. IOP was measured with air-puff tonometry at baseline, 30 min, 4 h, and 24 h post-laser. Baseline characteristics were comparable. In the dexmedetomidine group, mean IOP values were 16.3 ± 3.6, 14.8 ± 4.7, 17.1 ± 6.2, and 16.7 ± 4.5 mmHg, while in the brimonidine group, they were 16.7 ± 2.9, 13.3 ± 3.9, 13.2 ± 5.5, and 14.2 ± 3.9 mmHg, respectively. At 30 min, brimonidine significantly reduced IOP (p = 0.000), whereas dexmedetomidine did not (p = 0.116). At 4 and 24 h, IOP increased above baseline with dexmedetomidine but decreased with brimonidine (p = 0.001 and p = 0.004). Dexmedetomidine was associated with more IOP spikes > 10 mmHg (9% vs. 2%, p = 0.035) and IOP > 30 mmHg (7% vs. 2%, p = 0.09). No systemic or ocular side effects occurred. Although dexmedetomidine prevented acute IOP surges, its efficacy was inferior to brimonidine. Further studies should explore optimal dosing, formulations, and long-term safety to clarify its prophylactic potential.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 3","pages":"e70227"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13239948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148034034","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":"Evaluating the Educational Value of Artificial Intelligence in Pharmacotherapy Education.","authors":"Mariëlle G Hartjes, Michiel J Bakkum, Milan C Richir, Michiel A van Agtmael, Jelle Tichelaar","doi":"10.1002/prp2.70266","DOIUrl":"10.1002/prp2.70266","url":null,"abstract":"<p><p>Final-year medical students frequently make prescribing errors, partly because they have had insufficient training in therapeutic reasoning. Students need to understand the underlying rationale behind a drug choice in order to subsequently apply that knowledge critically and independently. Artificial intelligence (AI) models are becoming increasingly popular among students for therapeutic case solving, but the educational value of these models remains unclear. Therefore, the reasoning process of ChatGPT 3.5 (a general AI model) and EvidenceHunt basic (a specialized medical AI model) was compared with that of a medical specialist/clinical pharmacologist, according to the WHO 6-step. Although both AI models proposed reasonable treatment options, notable differences from those of the medical specialist were observed. The AI models tended to focus primarily on pharmacological recommendations for the main clinical problem, giving less consideration to broader contextual factors, such as the severity of illness. Some inaccuracies and illogical therapeutic alternatives were also identified. While AI models, such as ChatGPT and EvidenceHunt, show potential to improve education in therapeutic reasoning by suggesting plausible treatment options, their reasoning remains limited. They often justify rather than critically evaluate treatment choices, which restricts their depth, especially when it comes to considering alternative therapies and complex patient factors. For AI to be of real educational benefit, students will need to develop reflective skills so that they can critically appraise AI recommendations instead of passively accepting them. Teachers can encourage this by asking students to explain their treatment choices, thereby helping them to strengthen these skills.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 3","pages":"e70266"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13239473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147982665","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":"Pharmacologic MRI Brain Imaging Studies of Serotonin 5-HT₁ Receptor Agonists in Awake Mice.","authors":"Brittany M Brems, Erin E Sullivan, Ryan P McGlynn, Praveen Kulkarni, Craig F Ferris, Raymond G Booth","doi":"10.1002/prp2.70199","DOIUrl":"10.1002/prp2.70199","url":null,"abstract":"<p><p>Serotonin (5-hydroxytryptamine, 5-HT) type-1 G protein-coupled receptors are expressed throughout the central nervous system. 5-HT_1AR activation is the putative mechanism of approved drugs for generalized anxiety disorder and major depressive disorder and is being studied in the treatment of autism and neurological disorders. The 5-HT_1B and 5-HT_1DRs are the putative therapeutic targets for \"triptan\"-type migraine drugs, and the 5-HT_1BR is associated with prosocial effects, relative to autism treatment, consistent with its high expression in limbic and cortical brain regions. Under study is a recently developed drug candidate for autism, (S)-5-(2'-fluorophenyl)-2-dimethylaminotetralin (FPT), that is a full efficacy pan-5-HT₁R agonist (pEC50 = 7.4, 9.4, and 8.6 at 5-HT1_A, 5-HT1_B, and 5-HT1_DRs, respectively). FPT demonstrates anti-seizure, anxiolytic, and prosocial properties, as well as reduces stereotypic movements in Fmr1 knockout mice, a model for autism. The goal of this study was to compare brain activation patterns of the pan-5-HT₁R agonist FPT to NLX-112, a highly selective 5-HT_1AR full agonist (pEC₅₀ = 7.5) which also prevents seizures in Fmr1 knockout mice, to help establish therapeutic mechanisms in autism. We used pharmacological magnetic resonance imaging (phMRI) in awake C57BL/J6 mice to assess activation of integrated neuronal circuits as measured by blood oxygen level dependent volume of activation changes, comparing dose-related effects of FPT and NLX-112. The selective 5HT_1AR agonist NLX-112 broadly inhibited brain activity in a dose-dependent manner. In contrast, FPT increased global brain activity; however, dose-related effects were complex, suggesting FPT's polypharmacology at 5-HT₁Rs and perhaps other receptors are involved in its brain activation pattern.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 3","pages":"e70199"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13106894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147778146","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 Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Highly Selective NaV1.8 Inhibitor JKN2306 in Healthy Chinese Subjects.","authors":"Ying Yang, Mai Han, Gang Cui, Dan Zhang, Wei Wu, Na Mi, Jiangli Jin, Shuxiao Zhang, Xin Zhang, Junjie Li, Chunyan Xiao, Jing Wang, Chaoyun Gou, Chong Su, Jintong Li","doi":"10.1002/prp2.70277","DOIUrl":"10.1002/prp2.70277","url":null,"abstract":"<p><p>JKN2306 is a novel, highly selective Nav1.8 inhibitor under development for the treatment of acute pain. This first-in-human study aimed to evaluate its safety, tolerability, pharmacokinetics, and food effect (FE). This was a single center, randomized, double-blind, placebo controlled, single ascending dose (SAD) and FEstudy in healthy Chinese subjects. In the SAD part, 44 subjects were randomized to receive a single oral dose of JKN2306 (10, 30, 100, 200, or 400 mg) or placebo. The FE part was a sequential, two-period crossover study in 14 subjects from the 200 mg SAD cohort, who received a single 200 mg dose under fasting and fed conditions. Forty-four subjects were enrolled and completed the study. JKN2306 was safe and well-tolerated across all doses. Treatment-emergent adverse events were mostly Grade 1, with no serious adverse events or dose limiting toxicities. No clinically significant effects on QTc interval were observed. JKN2306 was rapidly absorbed, with T_max of 1.50-2.50 h. The t_1/2 ranged from 13.93 to 29.82 h. Exposure (C_max and AUC) increased approximately linearly with dose over the 10-400 mg range. Food intake delayed the median T_max by 1 h and reduced C_max by about 17%, but had no significant effect on AUC. JKN2306 exhibits a favorable safety and tolerability profile and predictable linear PK in healthy subjects. Food has a modest effect on the rate but not the extent of absorption. These findings support the further clinical development of JKN2306 for the treatment of acute pain. Trial Registration: chinadrugtrials.org.cn identifier: CTR20250247 and clinicaltrials.gov identifier: NCT07412938.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 3","pages":"e70277"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13266278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252785","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":"Age-Dependent Differences in Canakinumab Safety: A Comprehensive Pharmacovigilance Analysis Using the FAERS Database.","authors":"Youyang Wang, Ngasin Lam, Xiaoming Huang, Yang Jiao","doi":"10.1002/prp2.70251","DOIUrl":"10.1002/prp2.70251","url":null,"abstract":"<p><p>While the efficacy of canakinumab, an anti-interleukin-1β monoclonal antibody, is well-established, its safety profile, particularly across different age groups, remains inadequately explored. Using the FDA Adverse Event Reporting System (FAERS) database, this study evaluated postmarketing safety by analyzing adverse event (AE) reports from 2010 onward, with canakinumab as the primary suspected drug. Disproportionality analysis employed four algorithms-reporting odds ratio (ROR), proportional reporting ratio, multi-item gamma Poisson shrinker, and Bayesian confidence propagation neural network-to detect safety signals, and the Weibull distribution was used to model the temporal risk of AEs. 9262 canakinumab-related AE reports were analyzed. Significant signals were detected across multiple system organ classes (SOCs), most prominently general disorders and administration site conditions (n = 6765; ROR 1.47) and infections and infestations (n = 3532; ROR 2.54). Age-stratified analyses revealed distinct AE profiles: pyrexia, inappropriate schedule or dose of administration, and gastrointestinal and hepatobiliary disorders (e.g., abdominal pain, hepatitis) were most frequently reported in individuals < 12 years, as well as leukopenia in adolescents (12-17 years). Older patients (≥ 65 years) most frequently reported pneumonia, sepsis, and cellulitis, with strong signals for neoplasms. Temporal analysis revealed an early failure pattern, but ~40% of AEs occurred after 1 year. These findings underscore significant safety signals associated with canakinumab, including infections, gastrointestinal/hepatobiliary disorders in children, and neoplasms in older patients. The dual temporal pattern of AEs underscores the need for both short- and long-term surveillance.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 3","pages":"e70251"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13090527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717762","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}