Pharmacology Research & Perspectives最新文献

{"title":"Short-Term Oral Administration of the Porcupine Inhibitor, Wnt-c59, Improves the Structural and Functional Features of Experimental HFpEF.","authors":"Mhairi A Paul, Cherry L Wainwright, Emma E Hector, Erik Ryberg, Stephen J Leslie, Sarah K Walsh","doi":"10.1002/prp2.70054","DOIUrl":"10.1002/prp2.70054","url":null,"abstract":"<p><p>Heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of heart failure cases globally, and this incidence is increasing due to extended lifespans and accumulating comorbidities. Emerging evidence suggests that Wnt signaling plays a role in cardiomyocyte hypertrophy and cardiac fibrosis, which are key features of HFpEF. Furthermore, Porcupine (PORCN) inhibitors, which negatively regulate Wnt signaling, have shown promising results in improving cardiac function and reducing cardiac hypertrophy and/or fibrosis. This study investigated whether acute oral administration of the PORCN inhibitor, Wnt-c59, alters the maladaptive structural and/or functional features in a mouse model of HFpEF. Male mice were given a high-fat diet and L-NAME (0.5 g L^-1) in drinking water for 5 weeks, followed by a 2-week intervention of orally administered Wnt-c59 (5 mg kg^-1 day^-1). HFpEF mice were characterized by hypertension, cardiac hypertrophy and fibrosis, and diastolic dysfunction, although there was no evidence of activation of Wnt signaling in the heart. Despite this, short-term treatment of HFpEF mice with Wnt-c59 ameliorated adverse cardiac remodeling by increasing the ratio of the more compliant collagen type 3 to that of the more tensile collagen type 1 in the heart. Furthermore, Wnt-c59 also improved diastolic dysfunction, which was associated with the increased cardiac expression of brain natriuretic peptide, a known promoter of ventricular compliance. Our findings demonstrate that even short-term administration of a PORCN inhibitor improves both the structural and functional features of experimental HFpEF.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 1","pages":"e70054"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915283","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 Potential Drug-Drug Interactions for Novel Oral Melanocortin-1 Receptor Agonist Dersimelagon.","authors":"Akihito Ogasawara, Ryosuke Ide, Shinsuke Inoue, Minoru Tsuda, Renli Teng","doi":"10.1002/prp2.70069","DOIUrl":"10.1002/prp2.70069","url":null,"abstract":"<p><p>Dersimelagon is a novel investigational orally administered selective agonist of the melanocortin-1 receptor. The drug-drug interaction (DDI) potential of dersimelagon was investigated in both nonclinical (in vitro) and clinical studies. The in vitro inhibition of CYP/UGT isoforms and efflux/uptake transporters by dersimelagon was assessed. The impact of 300-mg dersimelagon on the pharmacokinetics (PK) of substrate drugs and the effect of co-administering verapamil on 100-mg dersimelagon PK (as substrate drug) were investigated in healthy participants in a Phase 1 study. DDIs were assessed based on ratios of C_max and AUC_0-∞ of substrate drug administered alone and with dersimelagon (or verapamil). Relatively potent in vitro inhibition of CYP2C9, CYP3A, UGT1A1, BCRP, P-gp, and OATPs by dersimelagon was observed. In the clinical study, exposures of atorvastatin (CYP3A, P-gp, BCRP, OATP substrate) rosuvastatin (BCRP and OATP substrate), and β-hydroxy simvastatin (metabolite of simvastatin) increased 2- to 3-fold (atorvastatin: C_max LS mean ratio = 198.0%; AUC_0-∞ ratio = 196.6%; rosuvastatin: C_max ratio = 316.5%, AUC_0-∞ ratio = 206.0%) when co-administered with dersimelagon. Midazolam (CYP3A substrate), digoxin (P-gp), pravastatin (OATP), and simvastatin (CYP3A) did not show any clinically relevant DDI effects when co-administered with dersimelagon. Dersimelagon exposure increased ~25% when co-administered with verapamil, an effect not considered clinically relevant. Dersimelagon 300 mg did not elicit major DDIs involving CYP/UGT enzymes and drug transporters; however, dersimelagon may have potential for clinically relevant DDIs with drugs that are substrates for BCRP, such as atorvastatin and rosuvastatin, and caution should be exercised when co-administering 300-mg dersimelagon with these statin drugs. Trial Registration: ClinicalTrials.gov: NCT04793295, NCT04402489, NCT04440592, NCT02834442, NCT03520036, NCT03503266.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 1","pages":"e70069"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066275","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":"What do We Mean by an Inclusive Pharmacology Education?","authors":"Jennifer Koenig, Steven Tucker","doi":"10.1002/prp2.70050","DOIUrl":"10.1002/prp2.70050","url":null,"abstract":"","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 1","pages":"e70050"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics and brain uptake of sodium selenate and selenium in naïve rats and a lateral fluid percussion injury rat model.","authors":"Chenxu Li, Pablo M Casillas-Espinosa, Patricia Grandizoli Saletti, Tina Chi, Glenn Yamakawa, Juliana Silva, Matt Hudson, Wei Liu, Nigel C Jones, Sandy R Shultz, Idrish Ali, Usha Mishra, James C Cloyd, Solomon L Moshe, Aristea S Galanopoulou, Terence J O'Brien, Lisa D Coles","doi":"10.1002/prp2.1256","DOIUrl":"10.1002/prp2.1256","url":null,"abstract":"<p><p>Post-traumatic epilepsy (PTE) is a life-long complication of traumatic brain injury (TBI). The development of PTE is associated with neurological morbidity and increases the risk of mortality. An aim of EpiBioS4Rx (Epilepsy Bioinformatics Study for Antiepileptogenic Therapy) was to test potential therapies to prevent the development of PTE in the lateral fluid percussion injury (LFPI) rat model of TBI, in which rats were subjected to injury at the left parietal cortex. Sodium selenate has been reported to be antiepileptogenic post-TBI in rodent models by activating protein phosphatase 2A and reducing phosphorylated tau (p-tau) protein. We aimed to characterize the pharmacokinetics (PK) and brain uptake of sodium selenate using naïve control and LFPI rats. Rats received either a single bolus dose or a single bolus dose followed by a 7-day subcutaneous minipump infusion of sodium selenate. Sodium selenate and selenium concentrations in plasma and brain were analyzed and used for PK estimation and brain exposure assessment. Selenium concentrations rapidly increased after sodium selenate administration, demonstrating biotransformation from sodium selenate to selenium. Sodium selenate and selenium PK parameters were estimated using non-compartmental analysis. Sodium selenate clearance (CL/F) and volume of distribution (V_d/F) varied by dose and route of administration, suggesting differences in bioavailability and nonlinear pharmacokinetics at the doses tested. Brain-to-plasma partition coefficients (AUC_brain/AUC_plasma) for sodium selenate and selenium were found to be 0.7-1.3 and 0.1-0.3 following single-dose injection, respectively, indicating active transport of sodium selenate across the blood-brain barrier (BBB).</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 6","pages":"e1256"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591118","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 Hepatic Metabolism Input Parameters Support Toxicokinetic Simulations for the Formation of Methoxy Propionic Acid From β-Isomer Propylene Glycol Methyl Ether.","authors":"Sophie Werner, Lucie Hegg, Nancy B Hopf, Myriam Borgatta, Laura Suter-Dick","doi":"10.1002/prp2.70037","DOIUrl":"10.1002/prp2.70037","url":null,"abstract":"<p><p>Propylene glycol ethers (PGEs) are organic solvents commonly found as technical grade on the commercial market, as mixtures of secondary (α-isomer) and primary (β-isomer, generally < 5%) alcohols. After handling products containing PGEs, they readily enter the human body where they are metabolized. The minor β-isomer is oxidized by alcohol dehydrogenase (ADH) followed by aldehyde dehydrogenase (ALDH) to a potentially harmful metabolite. Although the enzymatic rate is needed to estimate both parent and metabolite internal exposures, kinetic data for many PGEs are still scarce. Therefore, we generated in vitro hepatic intrinsic clearance data for propylene glycol methyl ether β-isomer (β-PGME) and its metabolite methoxy propionic acid (2-MPA) and integrated these data into an in silico toxicokinetic (TK) model. Hepatic clearance values for the model were generated using an established in vitro 3D culture of the human HepaRG cell line and human S9 liver fraction. Our results showed the presence of ADH and ALDH and consequently, the formation of 2-MPA in the 3D HepaRG and S9 fraction, which was slow to medium. We integrated the hepatic clearance values into the TK model to predict urinary 2-MPA concentrations. The simulated urinary 2-MPA concentrations fitted well (within twofold error from observed experimental data) for both liver systems, showing that they were both able to reliably predict the hepatic clearance of β-PGME. Although S9 is suitable for short-term studies, 3D cell culture models maintain metabolic competence over days and weeks. This opens the opportunity for long-term metabolism studies applying the 3D HepaRG model alone or in multi-organ systems.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 6","pages":"e70037"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801566","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":"Comparison of the Incidence and Magnitude of Hyponatremia Among Patients With Poststroke Depression Receiving Either Escitalopram or Sertraline.","authors":"Lina Naseralallah, Zahra Noureddine, Somaya Koryash","doi":"10.1002/prp2.70041","DOIUrl":"10.1002/prp2.70041","url":null,"abstract":"<p><p>Depression is the most frequent psychiatric condition experienced in stroke survivors. Selective serotonin reuptake inhibitors (SSRIs) are frequently used as first-line antidepressants; however, they have been strongly associated with hyponatremia which, in poststroke patients, can worsen outcomes. This study aims to determine and compare the incidence and magnitude of hyponatremia and potential risk factors in patients receiving either escitalopram or sertraline for the management of poststroke depression (PSD). A retrospective observational study involving all hospitalized patients who received either escitalopram or sertraline for the treatment of PSD. Electronic medical records were reviewed over a 5-year period with data collected on various demographic, laboratory, comorbidity, and medication-related variables. Data were analyzed using multivariate logistic regression. A total of 401 patients met the inclusion criteria. Overall, 36.7% of patients experienced hyponatremia, with 67 (38.3%) cases in patients receiving escitalopram and 76 (33.6%) in sertraline group. The median drop in sodium level from baseline was 5 mmol/L in both groups; with the majority of cases being of mild nature (73.1% and 69.7% for escitalopram and sertraline, respectively). Findings from the multivariate logistic regression did not yield a model with significant association (p = 0.353). Escitalopram and sertraline were both associated with an increased risk of hyponatremia in poststroke patients, with most cases being mild. There was no significant difference between treatment arms regarding the incidence or magnitude of hyponatremia. Caution should be exercised when prescribing escitalopram or sertraline.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 6","pages":"e70041"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770884","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":"Teneurin C-Terminal Associated Peptide (TCAP)-1 Attenuates Restraint Stress-Induced Corticosterone Increases in Male Mice and Rats.","authors":"Lauren E Mueller, Roseanne S Wexler, David A Lovejoy, Robert B Stein, Andrew M Slee","doi":"10.1002/prp2.70045","DOIUrl":"10.1002/prp2.70045","url":null,"abstract":"<p><p>Hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis response can result in anxiety and other neuropsychiatric disorders and effective therapeutics are needed to mitigate this maladaptive response. Here we examined the effects of Teneurin C-terminal Associated Peptide (TCAP)-1, a peptide known to inhibit corticotropin releasing factor (CRF)-mediated stress, on the physiological expression of stress, and whether the effects of TCAP-1 were dependent on the route of administration. We first examined whether subcutaneous administration of TCAP-1 influenced tube restraint stress-induced corticosterone (CORT) increases in both male mice and rats. Using a similar model, we further examined the efficacy and time course of intranasal TCAP-1. Results showed that subcutaneous TCAP-1 administration attenuated the expression of the physiological manifestation of stress in male mice and rats, and that intranasal TCAP-1 delivered prophylactically is effective at attenuating stress-induced CORT increases in male rats. These data indicate that TCAP-1 delivered though non-invasive routes of administration could have potential as a clinically relevant anxiolytic.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 6","pages":"e70045"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801585","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":"Enhancing Student Comprehension of Glucose Metabolism Visualization Through Virtual Simulation Platform: An Educational Approach.","authors":"Luna Ge, Tingting Feng, Shuo Cao, Hang Yin, Yuang Zhang, Jihong Pan, Wei Chen, Kai Cheng, Lin Wang","doi":"10.1002/prp2.70042","DOIUrl":"10.1002/prp2.70042","url":null,"abstract":"<p><p>With the rapid progression of biotechnology, the significance translational research on glycolysis in molecular pharmacology has become increasingly evident. To deepen students' understanding of glycolytic processes and facilitate their comprehension of drug action mechanisms, we have developed a visual virtual simulation platform dedicated glycolysis. The educational approach commenced with theoretical lectures on glycolysis, followed by practical laboratory sessions where students measured glycolysis-related parameters such as hexokinase, pyruvate kinase, and lactate. Students then engaged with the virtual simulation training platform to explore glycolytic stress tests and positron emission tomography/computed tomography (PET/CT) imaging, with their progress tracked through an assessment mode. The study involved 67 s-year undergraduate students majoring in biomedical sciences, all of whom had received instruction in glucose metabolism theories and completed the associated questionnaires. The results showed that the students gained a deeper understanding of glycolysis and the clinical application of PET/CT imaging in the context of glycolysis. The majority also agreed that the integration of scientific and clinical cases in teaching is beneficial and that the project sparked their interest in scientific research. These findings align with existing literature that emphasizes the importance of innovative educational tools in enhancing student engagement and understanding of the underlying theories of the curriculum. This project designed an innovative glycolytic metabolism teaching system encompassing the monitoring of traditional glycolytic indicators, glycolytic stress tests, and PET/CT imaging based on glycolysis. The visual virtual simulation platform for glycolysis can serve as an innovative educational tool in the molecular pharmacology curriculum or other courses involving glycolysis, assisting students in deeply understanding the molecular mechanisms of glycolysis and its significance in disease and drug action.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 6","pages":"e70042"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11600983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731752","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 Blood-Brain Barrier Permeability, Cytotoxicity, and Activity of Potential Acetylcholinesterase Inhibitors: In Vitro and In Silico Study.","authors":"L M Maboko, A Theron, J-L Panayides, W Cordier, D Fisher, V Steenkamp","doi":"10.1002/prp2.70043","DOIUrl":"10.1002/prp2.70043","url":null,"abstract":"<p><p>Acetylcholinesterase inhibitors (AChEIs) remain the first-line treatment for Alzheimer's disease. However, these drugs are largely symptomatic and often associated with adverse effects. This study aimed to evaluate novel pharmacophores for their in vitro AChEI activity, blood-brain barrier (BBB) permeability, and cytotoxic potential, hypothesizing that a combination of AChEIs could enhance symptom management while minimizing toxicity. A library of 1453 synthetic pharmacophores was assessed using in vitro and in silico methods to determine their feasibility as an inhibitor of the AChE enzyme. An in-house miniaturized Ellman's assay determined acellular AChEI activities, while pharmacokinetic properties were evaluated using the SwissADME web tool. The combinational effects of in silico BBB-permeable pharmacophores and donepezil were examined using a checkerboard AChEI assay. Cytotoxicity of active compounds and their synergistic combinations was assessed in SH-SY5Y neuroblastoma and bEnd.5 cells using the sulforhodamine B assay. Cellular AChEI activity of active in silico BBB-permeable predicted compounds was determined using an SH-SY5Y AChE-based assay. An in vitro BBB model was used to assess the effect of compounds on the integrity of the bEnd.5 monolayer. Out of the screened compounds, 12 demonstrated 60% AChEI activity at 5 μM, with compound A51 showing the lowest IC₅₀ (0.20 μM). Five compounds were identified as BBB-permeable, with the donepezil-C53 combination at ¼IC₅₀ exhibiting the strongest synergy (CI = 0.82). Compounds A136 and C129, either alone or with donepezil, showed cytotoxicity. Notably, compound C53, both alone and in combination with donepezil, demonstrated high AChEI activity and promising BBB permeability, warranting further investigation.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 6","pages":"e70043"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801360","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":"Evidence-based safety profile of oral ketorolac in adults: Systematic review and meta-analysis.","authors":"Vicente Esparza-Villalpando, Gladys Ortiz-Barroso, David Masuoka-Ito","doi":"10.1002/prp2.70033","DOIUrl":"10.1002/prp2.70033","url":null,"abstract":"<p><p>The primary objective of the present review was to report the safety profile of oral ketorolac in adults using the systematic review and meta-analysis methodology based on clinical trials. The present study is a PRISMA-based systematic review and risk ratio (RR) meta-analysis of the adverse events reported in clinical trials that used oral ketorolac; the review includes 50 clinical trials. The RR for the comparison of a single intake of oral ketorolac versus placebo, including all types of adverse events, was RR = 2.59, IC95% (1.5102; 4.4360) with p = 0.02, the RR for the comparison of a multiple intakes of oral ketorolac versus placebo for all types of adverse events was RR = 1.39, IC95% (0.95; 2.05) with p = 0.093, the RR for the comparison of a single intake of oral ketorolac versus active drugs for all types of adverse events was RR = 0.61, IC95% (0.49; 0.77) with p < 0.0001, the RR for the comparison of multiple intakes of oral ketorolac versus active drugs for all types of adverse events was RR = 0.78, IC95%(0.65; 0.93) with p = 0.006. Multiple intakes of 5, 10, or 20 mg of oral ketorolac, in treatment over 1-10 days, do not increase the risk of adverse events compared to placebo and show a tendency to reduce the risk of adverse events compared to active drugs. When a single intake of ketorolac (5, 10, 20, or 30 mg) is compared to a placebo, the risk increases only for trivial and mild adverse events.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 6","pages":"e70033"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11584978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695766","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}