Pharmacology Research & Perspectives最新文献_第10页

Preclinical metabolism and the disposition of vornorexant/TS-142, a novel dual orexin 1/2 receptor antagonist for the treatment of insomnia. 用于治疗失眠症的新型双重奥曲肽 1/2受体拮抗剂 vornorexant/TS-142 的临床前代谢和处置。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2024-04-01 DOI: 10.1002/prp2.1183

Yoshihiro Konno, Shunsuke Kamigaso, Hidetoh Toki, Shuichi Terasaka, Hirohiko Hikichi, Hiromi Endo, Jun-Ichi Yamaguchi, Akiko Mizuno-Yasuhira

{"title":"Preclinical metabolism and the disposition of vornorexant/TS-142, a novel dual orexin 1/2 receptor antagonist for the treatment of insomnia.","authors":"Yoshihiro Konno, Shunsuke Kamigaso, Hidetoh Toki, Shuichi Terasaka, Hirohiko Hikichi, Hiromi Endo, Jun-Ichi Yamaguchi, Akiko Mizuno-Yasuhira","doi":"10.1002/prp2.1183","DOIUrl":"10.1002/prp2.1183","url":null,"abstract":"We investigated the metabolism and disposition of vornorexant, a novel dual orexin receptor antagonist, in rats and dogs, and clarified in vitro metabolite profiles in humans. Furthermore, we investigated the pharmacokinetics of active metabolites in rats and dogs and their CNS distribution in rats to elucidate its contribution to drug efficacy. [14 C]vornorexant was rapidly and mostly absorbed after the oral administration in rats and dogs. The drug-derived radioactivity, including metabolites, was distributed to major organs such as the liver, kidneys in rats, and was almost eliminated within 24 h post-dose in both species. Metabolite profiling revealed that main clearance mechanism of vornorexant was metabolism via multiple pathways by oxidation. The major circulating components were the cleaved metabolites (M10, M12) in rats, and the unchanged form in dogs, followed by M1, and then M3. Incubation with human hepatocytes resulted in formation of metabolites, including M1, M3, M10, and M12. The metabolic pathways were similar in all tested species. Resulting from the PK and CNS distribution of active metabolites (M1 and M3) with weaker pharmacological activity, the concentration of the unchanged form was higher than that of active metabolites in rat CSF and dog plasma, suggesting that the unchanged form mainly contributed to the drug efficacy. These findings demonstrate that vornorexant is absorbed immediately after administration, and vornorexant and its metabolites are rapidly and completely eliminated in rats and dogs. Thus, vornorexant may have favorable pharmacokinetic profiles as a hypnotic drug to provide rapid onset of action and minimal next-day residual effects in humans.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 2","pages":"e1183"},"PeriodicalIF":2.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10943176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140140586","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}

引用次数: 0

Evaluation of OCT2-mediated drug-drug interactions between ulotaront and metformin in subjects with schizophrenia. 在精神分裂症患者中评估 OCT2 介导的乌洛他隆与二甲双胍之间的药物相互作用。

IF 2.6 4区医学

Pharmacology Research & Perspectives Pub Date : 2024-04-01 DOI: 10.1002/prp2.1191

Guangqing Xiao, Hironobu Tsukada, Yu-Luan Chen, Lei Shi, Seth C Hopkins, Gerald R Galluppi

{"title":"Evaluation of OCT2-mediated drug-drug interactions between ulotaront and metformin in subjects with schizophrenia.","authors":"Guangqing Xiao, Hironobu Tsukada, Yu-Luan Chen, Lei Shi, Seth C Hopkins, Gerald R Galluppi","doi":"10.1002/prp2.1191","DOIUrl":"10.1002/prp2.1191","url":null,"abstract":"Ulotaront (SEP-363856) is a TAAR1 agonist, with 5-HT1A agonist activity, currently in clinical development for the treatment of schizophrenia. In vitro studies indicate ulotaront is an OCT2-specific inhibitor with IC50 of 1.27 μM. The primary objective of this study is to determine if a single dose of ulotaront affects the PK of metformin, an index substrate of OCT2, in subjects with schizophrenia. In a randomized, single-blind, 2-period crossover study, 25 adults with schizophrenia received a single dose of metformin-HCl 850 mg (approximately 663 mg metformin) with and without coadministration of 100 mg ulotaront. The plasma samples were analyzed by fully validated LC-MS/MS methods. The primary PK endpoints for metformin were AUCinf, AUClast, Cmax, and tmax. The highest-anticipated clinical dose of ulotaront (100 mg) had no statistically significant effect on the PK of a single dose of metformin based on Cmax and AUCinf. Geometric least squares mean ratios were 89.98% and 110.63%, respectively, with the 90% confidential interval (CI) for each parameter contained within 80%-125%. Median tmax was comparable across the treatments. Ulotaront does not act as a perpetrator of OCT2-mediated DDI against metformin. Co-administration of ulotaront is not expected to require dose adjustment of metformin or other drugs cleared by OCT2.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 2","pages":"e1191"},"PeriodicalIF":2.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10963303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288749","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}

引用次数: 0

Progress in the treatment of diabetic cardiomyopathy, a systematic review. 糖尿病心肌病治疗进展，系统回顾。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2024-04-01 DOI: 10.1002/prp2.1177

Yiyi Shou, Xingyu Li, Quan Fang, Aqiong Xie, Yinghong Zhang, Xinyan Fu, Mingwei Wang, Wenyan Gong, Xingwei Zhang, Dong Yang

{"title":"Progress in the treatment of diabetic cardiomyopathy, a systematic review.","authors":"Yiyi Shou, Xingyu Li, Quan Fang, Aqiong Xie, Yinghong Zhang, Xinyan Fu, Mingwei Wang, Wenyan Gong, Xingwei Zhang, Dong Yang","doi":"10.1002/prp2.1177","DOIUrl":"10.1002/prp2.1177","url":null,"abstract":"Diabetic cardiomyopathy (DCM) is a condition characterized by myocardial dysfunction that occurs in individuals with diabetes, in the absence of coronary artery disease, valve disease, and other conventional cardiovascular risk factors such as hypertension and dyslipidemia. It is considered a significant and consequential complication of diabetes in the field of cardiovascular medicine. The primary pathological manifestations include myocardial hypertrophy, myocardial fibrosis, and impaired ventricular function, which can lead to widespread myocardial necrosis. Ultimately, this can progress to the development of heart failure, arrhythmias, and cardiogenic shock, with severe cases even resulting in sudden cardiac death. Despite several decades of both fundamental and clinical research conducted globally, there are currently no specific targeted therapies available for DCM in clinical practice, and the incidence and mortality rates of heart failure remain persistently high. Thus, this article provides an overview of the current treatment modalities and novel techniques pertaining to DCM, aiming to offer valuable insights and support to researchers dedicated to investigating this complex condition.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 2","pages":"e1177"},"PeriodicalIF":2.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10895687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139972987","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}

引用次数: 0

Identification and neuroprotective properties of NA-184, a calpain-2 inhibitor. 钙蛋白酶-2抑制剂NA-184的鉴定和神经保护特性

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2024-04-01 DOI: 10.1002/prp2.1181

Michel Baudry, Yubin Wang, Xiaoning Bi, Yun Lyna Luo, Zhijun Wang, Zeechan Kamal, Alexander Shirokov, Ed Sullivan, Dennis Lagasca, Hany Khalil, Gary Lee, Kathy Fosnaugh, Philippe Bey, Shujaath Mehdi, Greg Coulter

{"title":"Identification and neuroprotective properties of NA-184, a calpain-2 inhibitor.","authors":"Michel Baudry, Yubin Wang, Xiaoning Bi, Yun Lyna Luo, Zhijun Wang, Zeechan Kamal, Alexander Shirokov, Ed Sullivan, Dennis Lagasca, Hany Khalil, Gary Lee, Kathy Fosnaugh, Philippe Bey, Shujaath Mehdi, Greg Coulter","doi":"10.1002/prp2.1181","DOIUrl":"10.1002/prp2.1181","url":null,"abstract":"Our laboratory has shown that calpain-2 activation in the brain following acute injury is directly related to neuronal damage and the long-term functional consequences of the injury, while calpain-1 activation is generally neuroprotective and calpain-1 deletion exacerbates neuronal injury. We have also shown that a relatively selective calpain-2 inhibitor, referred to as C2I, enhanced long-term potentiation and learning and memory, and provided neuroprotection in the controlled cortical impact (CCI) model of traumatic brain injury (TBI) in mice. Using molecular dynamic simulation and Site Identification by Ligand Competitive Saturation (SILCS) software, we generated about 130 analogs of C2I and tested them in a number of in vitro and in vivo assays. These led to the identification of two interesting compounds, NA-112 and NA-184. Further analyses indicated that NA-184, (S)-2-(3-benzylureido)-N-((R,S)-1-((3-chloro-2-methoxybenzyl)amino)-1,2-dioxopentan-3-yl)-4-methylpentanamide, selectively and dose-dependent inhibited calpain-2 activity without evident inhibition of calpain-1 at the tested concentrations in mouse brain tissues and human cell lines. Like NA-112, NA-184 inhibited TBI-induced calpain-2 activation and cell death in mice and rats, both male and females. Pharmacokinetic and pharmacodynamic analyses indicated that NA-184 exhibited properties, including stability in plasma and liver and blood-brain barrier permeability, that make it a good clinical candidate for the treatment of TBI.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 2","pages":"e1181"},"PeriodicalIF":2.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10907882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013133","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}

引用次数: 0

Effects of vasoactive substances on biomechanics of small resistance arteries of male and female Dahl salt-sensitive rats. 血管活性物质对雌雄达尔盐敏感大鼠阻力小动脉生物力学的影响

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2024-04-01 DOI: 10.1002/prp2.1180

Eric A Mensah, Noriko Daneshtalab, Reza Tabrizchi

{"title":"Effects of vasoactive substances on biomechanics of small resistance arteries of male and female Dahl salt-sensitive rats.","authors":"Eric A Mensah, Noriko Daneshtalab, Reza Tabrizchi","doi":"10.1002/prp2.1180","DOIUrl":"10.1002/prp2.1180","url":null,"abstract":"Changes in vascular biomechanics leading to increase in arterial stiffness play a pivotal role in circulatory dysfunction. Our objectives were to examine sex-specific pharmacological changes related to the biomechanics and any structural modifications in small resistance arteries of Dahl salt-sensitive male and female rats. The composite Young modulus (CYM) was determined using pressure myograph recordings, and immunohistochemistry was used for the evaluation of any structural changes in the third-order mesenteric arteries (n = 6). Animals on high-salt diet developed hypertension with significant elevation in central and peripheral blood pressures and pulse wave velocity compared to those on regular diet. There were no significant differences observed in the CYM between any of the groups (i.e., males and females) in vehicle-treated time-control studies. The presence of verapamil (0.3 μM) significantly reduced CYM in hypertensive males without changes within females compared to vehicle. This effect was abolished by phenylephrine (0.3 μM). BaCl2 (100 μM), ouabain (100 μM), and L-NAME (0.3 μM) combined significantly increased CYM in vessels from in normotensive males and females but not in hypertensive males compared to vehicle. The increase in CYM was abolished in the presence of phenylephrine. Sodium nitroprusside (0.3 μM), in the presence of phenylephrine, significantly reduced CYM in male normotensive versus hypertensive, with no differences within females. Significant differences were observed in immunohistochemical assessment of biomechanical markers of arterial stiffness between males and females. Our findings suggest sex possibly due to pressure differences to be responsible for adaptive changes in biomechanics, and varied pharmacological responses in hypertensive state.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 2","pages":"e1180"},"PeriodicalIF":2.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10902908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139990864","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}

引用次数: 0

Phenotype versus genotype to optimize cancer dosing in the clinical setting-focus on 5-fluorouracil and tyrosine kinase inhibitors. 表型与基因型在临床中优化癌症用药--聚焦 5-氟尿嘧啶和酪氨酸激酶抑制剂。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2024-04-01 DOI: 10.1002/prp2.1182

Jennifer H Martin, Peter Galettis, Alex Flynn, Jennifer Schneider

{"title":"Phenotype versus genotype to optimize cancer dosing in the clinical setting-focus on 5-fluorouracil and tyrosine kinase inhibitors.","authors":"Jennifer H Martin, Peter Galettis, Alex Flynn, Jennifer Schneider","doi":"10.1002/prp2.1182","DOIUrl":"10.1002/prp2.1182","url":null,"abstract":"Cancer medicines often have narrow therapeutic windows; toxicity can be severe and sometimes fatal, but inadequate dose intensity reduces efficacy and survival. Determining the optimal dose for each patient is difficult, with body-surface area used most commonly for chemotherapy and flat dosing for tyrosine kinase inhibitors, despite accumulating evidence of a wide range of exposures in individual patients with many receiving a suboptimal dose with these strategies. Therapeutic drug monitoring (measuring the drug concentration in a biological fluid, usually plasma) (TDM) is an accepted and well validated method to guide dose adjustments for individual patients to improve this. However, implementing TDM in routine care has been difficult outside a research context. The development of genotyping of various proteins involved in drug elimination and activity has gained prominence, with several but not all Guideline groups recommending dose reductions for particular variant genotypes. However, there is increasing concern that dosing recommendations are based on limited data sets and may lead to unnecessary underdosing and increased cancer mortality. This Review discusses the evidence surrounding genotyping and TDM to guide decisions around best practice.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 2","pages":"e1182"},"PeriodicalIF":2.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10907881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013134","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}

引用次数: 0

Evaluation of the cardiac safety of parsaclisib, a selective PI3Kδ inhibitor, in patients with previously treated B-cell malignancies: Results from the CITADEL-101 study 评估帕沙利西（一种选择性 PI3Kδ 抑制剂）对既往接受过治疗的 B 细胞恶性肿瘤患者的心脏安全性：CITADEL-101研究的结果

IF 2.6 4区医学

Pharmacology Research & Perspectives Pub Date : 2024-02-26 DOI: 10.1002/prp2.1165

Jia Li, Xiaohua Gong, Xing Liu, Xiang Liu, Ke Szeto, Xuejun Chen

{"title":"Evaluation of the cardiac safety of parsaclisib, a selective PI3Kδ inhibitor, in patients with previously treated B-cell malignancies: Results from the CITADEL-101 study","authors":"Jia Li, Xiaohua Gong, Xing Liu, Xiang Liu, Ke Szeto, Xuejun Chen","doi":"10.1002/prp2.1165","DOIUrl":"https://doi.org/10.1002/prp2.1165","url":null,"abstract":"Parsaclisib, a potent and selective phosphatidylinositol 3 kinase δ inhibitor, has been investigated for the treatment of B-cell malignancies and studied in patients with autoimmune diseases and myelofibrosis. The CITADEL-101 study (NCT02018861) assessed safety, tolerability, and preliminary efficacy of parsaclisib in patients with relapsed or refractory non-Hodgkin lymphoma. This study evaluated the cardiac safety of parsaclisib as monotherapy based on data from 72 patients enrolled in the CITADEL-101 study. Time-matched pharmacokinetic and ECG measurements were collected at specified times for 69 patients receiving monotherapy in doses of 5, 10, 15, 20, 30, and 45 mg once daily. Based on the categorical outlier analysis, no dose-dependent effect was observed on the incidence of outliers in QT interval corrected for heart rate (HR) by Fridericia's method (QTcF), HR, or cardiac conduction. Based on central tendency analysis, the least square means (LSMs) (90% confidence interval [CI]) of ΔQTcF from the central tendency analysis ranged from −6.83 (−18.8 to 5.19) to 4.75 ms (0.410–9.09) across dose groups (below 20 ms, the threshold of large QT effects) and was not considered dose dependent. Moreover, the LSMs of ΔHR, ΔPR interval, and ΔQRS interval were minor. From the concentration-ΔQTcF analyses, the predicted ΔQTcF (90% CI) for all dose levels was between 0.365 (−1.75 to 2.48) and 7.87 ms (0.921–14.8), with the highest upper limit of CIs well below 20 ms, and therefore, a large QT/QTc effect was ruled out up to the highest dose level (45 mg) investigated. Overall, parsaclisib at the dose ranges studied did not reveal concentration-dependent effects on change in QTcF and did not have a significant effect on HR or cardiac conduction.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"27 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139968334","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}

引用次数: 0

Real-world treatment outcomes of immune checkpoint inhibitors used off-label in oncology: A comprehensive cancer institution experience. 免疫检查点抑制剂在肿瘤学中标示外使用的实际治疗效果：综合癌症机构的经验。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2024-02-01 DOI: 10.1002/prp2.1167

Sandra Fontanals, Anna Esteve, Andrea González, Cristina Ibáñez, Ricard Mesía, Ana Clopés

{"title":"Real-world treatment outcomes of immune checkpoint inhibitors used off-label in oncology: A comprehensive cancer institution experience.","authors":"Sandra Fontanals, Anna Esteve, Andrea González, Cristina Ibáñez, Ricard Mesía, Ana Clopés","doi":"10.1002/prp2.1167","DOIUrl":"10.1002/prp2.1167","url":null,"abstract":"Off-label use (OLU) is quite common in oncology due to the complexity of cancer and the time-consuming regulatory process. However, outcomes of OLU in cancer treatment remain unclear. This study aimed to evaluate the overall survival (OS), event-free survival (EFS), duration of treatment (DOT), and reason for treatment discontinuation in patients receiving immune checkpoint inhibitors (ICI) as OLU for solid tumors from 2011 to 2020. The study collected data on 356 episodes (353 patients), with a median age of 64.4 years, 36.2% women, and 14.6% ECOG ≥ 2. Median OS was 15.7 (11.9-18.7) months, and median EFS was 5.4 (3.8-6.6) months. Men, patients with metastatic disease or ECOG-PS higher than 1, had worse survival outcomes. The findings derived from this study provide valuable information regarding the real-world use of ICI-OLU and contributes to enhancing the decision-making process for individuals with cancer. Further research on immunotherapy outcomes of OLU in cancer is needed.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 1","pages":"e1167"},"PeriodicalIF":2.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10775181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139404000","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}

引用次数: 0

Pharmacology education in the medical curriculum: Challenges and opportunities for improvement. 医学课程中的药理学教育：挑战与改进机会。

IF 2.6 4区医学

Pharmacology Research & Perspectives Pub Date : 2024-02-01 DOI: 10.1002/prp2.1178

Pius S Fasinu, Teresa W Wilborn

{"title":"Pharmacology education in the medical curriculum: Challenges and opportunities for improvement.","authors":"Pius S Fasinu, Teresa W Wilborn","doi":"10.1002/prp2.1178","DOIUrl":"10.1002/prp2.1178","url":null,"abstract":"The knowledge and application of pharmacology is essential for safe prescribing and administration of drugs. In this narrative review, the challenges to pharmacology education in the medical curricula were broadly identified to include issues around content and pedagogies. The increasing number of approved drugs and drug targets, expanding field of pharmacology and the often-changing treatment guidelines and board-defined competencies can make pharmacology education in the medical curriculum daunting. There has been a consensus around the deployment of innovative medical curricula with emphasis on vertical and horizontal integration. This strategy, effective as it has been, presents new challenges to pharmacology education. As a discipline often perceived by students to be hard-to-learn, the future of pharmacology education must include heavy reliance on active learning strategies. The continuing utilization of problem-based, team-based and case-based learning can be complemented with personalized learning which aims to identify the learning gaps in individual students. Technology-inspired student engagement can foster pharmacology learning and retention. Early exposure to pharmacology from premedical preparation through an enduring across-the-level integration can be an effective way to enhance pharmacology learning in the medical curricula.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 1","pages":"e1178"},"PeriodicalIF":2.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10869893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139741733","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}

引用次数: 0

Is pitolisant safe for clinical use? A retrospective pharmacovigilance study focus on the post-marketing safety. 匹多莫德临床使用安全吗？一项以上市后安全性为重点的回顾性药物警戒研究。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2024-02-01 DOI: 10.1002/prp2.1161

Cheng Jiang, Jiancheng Qian, Xin Jiang, Shuohan Zhang, Junxian Zheng, Hongwei Wang

{"title":"Is pitolisant safe for clinical use? A retrospective pharmacovigilance study focus on the post-marketing safety.","authors":"Cheng Jiang, Jiancheng Qian, Xin Jiang, Shuohan Zhang, Junxian Zheng, Hongwei Wang","doi":"10.1002/prp2.1161","DOIUrl":"10.1002/prp2.1161","url":null,"abstract":"Pitolisant, a novel histamine H3-receptor antagonist, holds significant promise for treating narcolepsy. However, a petition, which highlighted that pitolisant was associated with deaths during clinical trials, has propelled it into the spotlight of widespread societal attention on April 3, 2023. Till now, the clinical safety of pitolisant remains a heatedly debated topic. This study aimed to offer a comprehensive assessment of the safety profile of pitolisant in real-world clinical settings. Adverse event reports where pitolisant was the primary suspect drug were extracted from the FDA Adverse Event Reporting System database. The clinical characteristics and concomitant drugs of the pitolisant-associated adverse events were analyzed. The potential adverse event signals of pitolisant were explored using four disproportionality analysis methods. Furthermore, the difference in pitolisant-associated adverse event signals was investigated concerning sex, age, weight, and dose. A total of 526 reports and 1695 adverse events with pitolisant as the primary suspected drug were identified. The most significant adverse event signals were generally mild and of short duration. The concomitant drugs of pitolisant were highly intricate, mainly included drugs for treating narcolepsy as well as antidepressants. Seven new significant adverse event signals emerged. The safety profile of pitolisant exhibited no significant differences across age and dose groups, although slight variations were observed in relation to sex and weight. The findings from reports of death and life-threatening outcomes underscore the importance of enhanced monitoring for cardiac and respiratory adverse reactions when utilizing pitolisant. This study provided a broader understanding of the safety profile of pitolisant.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 1","pages":"e1161"},"PeriodicalIF":2.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10765455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139088002","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}

引用次数: 0