Pharmacology Research & Perspectives最新文献

{"title":"How to approach a study in ethnopharmacology? Providing an example of the different research stages for newcomers to the field today.","authors":"Fabien Schultz,&nbsp;Leif-Alexander Garbe","doi":"10.1002/prp2.1109","DOIUrl":"https://doi.org/10.1002/prp2.1109","url":null,"abstract":"<p><p>Ethnopharmacology seeks to investigate humankind's use of natural materials, such as plants, fungi, microorganisms, animals, and minerals, for medicinal purposes. In this highly interdisciplinary field, which can be described as a bridge between the natural/medical and socio-cultural sciences, pharmacological, anthropological, and socio-cultural research methods are often applied, along with methods from other branches of science. When entering the field of ethnopharmacology as a newcomer, student, or early career researcher today, the tremendous amount of scientific publications, and even classical books from this field and related scientific disciplines, can be overwhelming. Ethnopharmacology has evolved over the past decades, and new key topics, such as the decolonization of the field, issues on intellectual property and benefit-sharing, species conservation, the preservation of traditional knowledge, the protection of indigenous communities, science outreach, and climate change, have become important and urgent aspects of the field that must not be disregarded by today's ethnopharmacologists. One of the questions of newcomers will be, \"Where to begin?\" This review article offers a brief (and certainly not comprehensive) introduction to the science of ethnopharmacology, highlighting some of its past most notable achievements and future prospects. In addition, this article provides an example for newcomers to the field of how to address different stages that may be involved in conducting ethnopharmacological field and lab studies, including early-stage drug discovery and community work. The example presented summarizes a series of studies conducted in the remote Greater Mpigi region of Uganda, located in East Africa. Stages of ethnopharmacological research described include ethnobotanical surveying and fieldwork, the pharmacological assessment of activity with diverse targets in the laboratory, and the transfer of results back to indigenous communities, that is, non-financial benefit sharing as a potential best practice example. As a result of this research example, a total of six original research articles have been published on the medicinal application and ethnopharmacology of 16 plant species from the Ugandan study site, offering a large quantity of results. These six publications reflect the multifaceted nature of the interdisciplinary science of ethnopharmacology, which may serve as a reference point and inspiration for newcomers to design and conduct their own independent ethnopharmacological research endeavors at other study sites. Major bottlenecks and solutions are provided, and the current social media channels with educational ethnopharmacological content are briefly introduced.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b9/c6/PRP2-11-e01109.PMC10375576.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9895647","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":"Delineation of the distinct inflammatory signaling roles of TAK1 and JAK1/3 in the CIA model of rheumatoid arthritis.","authors":"Robert Freeze,&nbsp;Kelly W Yang,&nbsp;Timothy Haystead,&nbsp;Philip Hughes,&nbsp;Scott Scarneo","doi":"10.1002/prp2.1124","DOIUrl":"10.1002/prp2.1124","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a complex autoimmune disease characterized by hyperactive immune cells within the joints, which leads to inflammation, bone degeneration, and chronic pain. For several decades, frontline immunomodulators such as the anti-tumor necrosis factor (TNF) biologics adalimumab (Humira), etanercept (Enbrel), and infliximab (Remicade) have successfully managed disease progression for many patients. However, over time, patients become refractory to these treatments requiring chronic disease to be managed with conventional and more problematic disease modifying antirheumatic drugs such as methotrexate and hydroxychloroquine, and corticosteroids. Due to the large proportion of patients who continue to fail on frontline biologic therapies, there remains an unmet need to derive novel alternative targets with improved efficacy and safety profiles to treat RA. Recent advances in the field have defined novel targets that play important roles in RA pathology, including the Janus activated kinase (JAK) and transforming growth factor beta activated kinase-1 (TAK1). Although three inhibitors of the JAK signaling pathway have been approved for the treatment of moderately to severely active RA in patients who failed on one or more anti-TNFs, at present, no FDA approved TAK1 treatments exist. Our recent discovery of a highly potent and selective, orally bioavailable TAK1 inhibitor has provided insight into the therapeutic potential of this protein kinase as a novel target for RA. Here, we show the distinct cytokine signaling of tofacitnib (Xeljanz; JAK1/3 inhibitor) compared to HS-276 (TAK1 inhibitor) in lipopolysaccharide (LPS) challenged THP-1 cells. Furthermore, in the collagen induced arthritis pre-clinical mouse model of RA, both tofacintib and HS-276 attenuated disease activity score and inflammatory cytokines in the serum. Overall, our results delineate the distinct cytokine signaling of JAK1/3 and TAK1 targeted therapies in vitro and in vivo and suggest that selective TAK1 inhibitors may provide superior therapeutic relief in RA with fewer adverse events.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9f/9f/PRP2-11-e01124.PMC10415874.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9997425","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":"Oral morphine induces spinal 5-hydroxytryptamine (5-HT) release using an opioid receptor-independent mechanism.","authors":"Shingo Nakamura,&nbsp;Shuji Komatsu,&nbsp;Toshihiko Yamada,&nbsp;Hiromi Kitahara,&nbsp;Tatsuo Yamamoto","doi":"10.1002/prp2.1119","DOIUrl":"https://doi.org/10.1002/prp2.1119","url":null,"abstract":"<p><p>Morphine induces spinal 5-hydroxytryptamine (5-HT) release, but the role and mechanism of the spinal 5-HT release induced by morphine are not well understood. The purpose of this study was to define the role and mechanism of spinal 5-HT release induced by oral morphine. We also examined whether persistent pain affected the spinal 5-HT release induced by oral morphine. Spinal 5-HT release was measured using microdialysis of lumbar cerebrospinal fluid (CSF). Two opioids, morphine and oxycodone, were orally administered and 5-HT release was measured in awake rats. Naloxone and β-funaltrexamine (β-FNA) were used to determine whether the effect of morphine on 5-HT release was mediated by opioid receptor activation. To study persistent pain, a formalin test was used. At 45 min after oral morphine administration, the formalin test was started and spinal 5-HT release was measured. Oral morphine, but not oral oxycodone, increased 5-HT release at the spinal cord to approximately 4000% of the baseline value. This effect of morphine was not antagonized by either naloxone or β-FNA at a dose that antagonized the antinociceptive effect of morphine. Formalin-induced persistent pain itself had no effect on spinal 5-HT release but enhanced the oral morphine-induced spinal 5-HT release. Oral morphine-induced spinal 5-HT release was not mediated by opioid receptor activation. Spinal 5-HT induced by oral morphine did not play a major role in the antinociceptive effect of morphine in the hot plate test. Persistent pain increased oral morphine-induced spinal 5-HT release.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/48/dc/PRP2-11-e01119.PMC10366105.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10251121","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":"Experimental training in molecular pharmacology education based on drug-target interactions.","authors":"Luna Ge,&nbsp;Kai Cheng,&nbsp;Yuang Zhang,&nbsp;Junling Li,&nbsp;Wei Chen,&nbsp;Guanhua Song,&nbsp;Lin Wang","doi":"10.1002/prp2.1118","DOIUrl":"https://doi.org/10.1002/prp2.1118","url":null,"abstract":"<p><strong>Introduction: </strong>Drug development has been challenged by the dual drawbacks involving unpredictable disease outcomes and drug resistance, which has placed greater demands on pharmacology education. Molecular pharmacology, as a frontier crossover field of pharmacology, focuses on the research of new drugs and targets. However, due to the lack of a systematic experimental training system, molecular pharmacology has not made a corresponding contribution in promoting the training of innovative talent in pharmacology. We aim to establish an experimental training program suitable for molecular pharmacology to improve students' ability to engage in drug development in future.</p><p><strong>Methods: </strong>Based on the feasibility of drug-target projects, a comprehensive training program containing molecular docking, target stability experiment, and fluorescent probe detection of protein expression in living cells and mice was conducted among 20 pharmacy graduate students. The experimental training was assessed by the experimental training report and the student recognition questionnaires.</p><p><strong>Results: </strong>All 20 students mastered the experimental principles and operations required for the training program. The experimental reports proved that the students were in good command of the experimental principles, operations and applications. The results of the Likert questionnaire indicated that the training program promoted the understanding of the drug research process and increased motivation to learn.</p><p><strong>Conclusion: </strong>The designed experimental training program has a positive effect on the training of pharmacology talents, and can be implemented as a part of molecular pharmacology education.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1a/15/PRP2-11-e01118.PMC10405239.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9950491","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":"Modeling time-delayed concentration-QT effects with ACT-1014-6470, a novel oral complement factor 5a receptor 1 (C5a₁ receptor) antagonist.","authors":"Marion Anliker-Ort,&nbsp;Chih-Hsuan Hsin,&nbsp;Andreas Krause,&nbsp;Marc Pfister,&nbsp;John van den Anker,&nbsp;Jasper Dingemanse,&nbsp;Priska Kaufmann","doi":"10.1002/prp2.1112","DOIUrl":"https://doi.org/10.1002/prp2.1112","url":null,"abstract":"<p><p>The novel oral complement factor 5a receptor 1 antagonist ACT-1014-6470 was well tolerated in single- and multiple-ascending dose studies, including 24 h Holter electrocardiogram (ECG) recordings evaluating its cardiodynamics based on data from single doses of 30-200 mg and twice-daily (b.i.d.) dosing of 30-120 mg for 4.5 days. By-time point, categorical, and morphological analyses as well as concentration-QT modeling and simulations were performed. No relevant effect of ACT-1014-6470 on ECG parameters was observed in the categorical and morphological analyses. After single-dose administration, the by-time point analysis indicated a delayed dose-dependent increase in placebo-corrected change from baseline in QT interval corrected with Fridericia's formula (ΔΔQTcF) at >6 h postdose. After b.i.d. dosing, ΔΔQTcF remained elevated during the 24-h recording period, suggesting that the effect was not directly related to ACT-1014-6470 plasma concentration. The concentration-QT model described change from baseline in QTcF (ΔQTcF)-time profiles best with a 1-oscillator model of 24 h for circadian rhythm, an effect compartment, and a sigmoidal maximum effect model. Model-predicted ΔΔQTcF was derived for lower doses and less-frequent dosing than assessed clinically. Median and 90% prediction intervals of ΔΔQTcF for once-daily doses of 30 mg and b.i.d. doses of 10 mg did not exceed the regulatory threshold of 10 ms but would achieve ACT-1014-6470 plasma concentrations enabling adequate target engagement. Results from cardiodynamic assessments identified dose levels and dosing regimens that could be considered for future clinical trials, attempting to reduce QT liability.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/93/74/PRP2-11-e01112.PMC10357345.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9862417","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":"Role of efficacy as a determinant of locomotor activation by mu-opioid receptor (MOR) ligands in female and male mice. II. Effects of novel MOR-selective phenylmorphans with high-to-low MOR efficacy.","authors":"Edna J Santos,&nbsp;Nima Nassehi,&nbsp;Eric W Bow,&nbsp;Dana R Chambers,&nbsp;Eugene S Gutman,&nbsp;Arthur E Jacobson,&nbsp;Joshua A Lutz,&nbsp;Samuel A Marsh,&nbsp;Kenner C Rice,&nbsp;Agnieszka Sulima,&nbsp;Dana E Selley,&nbsp;S Stevens Negus","doi":"10.1002/prp2.1111","DOIUrl":"https://doi.org/10.1002/prp2.1111","url":null,"abstract":"<p><p>Low-efficacy mu-opioid receptor (MOR) agonists represent promising therapeutics, but existing compounds (e.g., buprenorphine, nalbuphine) span a limited range of low MOR efficacies and have poor MOR selectivity. Accordingly, new and selective low-efficacy MOR agonists are of interest. A novel set of chiral C9-substituted phenylmorphans has been reported to display improved MOR selectivity and a range of high-to-low MOR efficacies under other conditions; however, a full opioid receptor binding profile for these drugs has not been described. Additionally, studies in mice will be useful for preclinical characterization of these novel compounds, but the pharmacology of these drugs in mice has also not been examined. Accordingly, the present study characterized the binding selectivity and in vitro efficacy of these compounds using assays of opioid receptor binding and ligand-stimulated [³⁵ S]GTPɣS binding. Additionally, locomotor effects were evaluated as a first step for in vivo behavioral assessment in mice. The high-efficacy MOR agonist and clinically effective antidepressant tianeptine was included as a comparator. In binding studies, all phenylmorphans showed improved MOR selectivity relative to existing lower-efficacy MOR agonists. In the ligand-stimulated [³⁵ S]GTPɣS binding assay, seven phenylmorphans had graded levels of sub-buprenorphine MOR efficacy. In locomotor studies, the compounds again showed graded efficacy with a rapid onset and ≥1 h duration of effects, evidence for MOR mediation, and minor sex differences. Tianeptine functioned as a high-efficacy MOR agonist. Overall, these in vitro and in vivo studies support the characterization of these compounds as MOR-selective ligands with graded MOR efficacy and utility for further behavioral studies in mice.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/84/68/PRP2-11-e01111.PMC10307939.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10119116","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":"Impact of metformin on statin-associated myopathy risks in dyslipidemia patients.","authors":"Keunhyeong Bak,&nbsp;Suhyeon Moon,&nbsp;Minjung Ko,&nbsp;Yeo Jin Choi,&nbsp;Sooyoung Shin","doi":"10.1002/prp2.1114","DOIUrl":"https://doi.org/10.1002/prp2.1114","url":null,"abstract":"<p><p>A growing number of patients with metabolic disorders are receiving statin and antidiabetic therapies as comedications. A signal of increased risk of myotoxicity due to potential interactions between antidiabetics and statins has been detected in previous studies. To investigate the effects of metformin on myopathy risks when added to preexisting statin therapy in dyslipidemia patients, we performed a retrospective cohort study using the Korean national health insurance data in statin-treated dyslipidemia patients with or without concomitant metformin use. We compared the risk of myopathy in statin + metformin users against statin-only users. Hazard ratios (HRs) and 95% confidence intervals (CIs) have been calculated following propensity score (PS) matching between study groups and subsequent stratification per patient factors. We included 4092 and 8161 patients in PS-matched statin + metformin and statin-only groups, respectively. The risk of myopathy decreased when metformin was used together with statins (adjusted HR 0.84; 95% CI 0.71-0.99). In subgroup analyses per individual statin agent and in stratified risk analyses, no specific statin agents or patient factors were associated with statistically significant myopathy risk. This study found that a comedication with metformin was associated with decreased myopathy risk in statin-treated dyslipidemia patients compared to statin-only users. Our findings suggest that metformin may provide protective effects on potential muscle toxicities induced by statin therapy.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/23/44/PRP2-11-e01114.PMC10327420.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9862700","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":"An analysis of patterns of distribution of buprenorphine in the United States using ARCOS, Medicaid, and Medicare databases.","authors":"Zhi-Shan Hsu,&nbsp;Justina A Warnick,&nbsp;Tice R Harkins,&nbsp;Briana E Sylvester,&nbsp;Neal K Bharati,&nbsp;leTausjua B Eley,&nbsp;Stephanie D Nichols,&nbsp;Kenneth McCall,&nbsp;Brian J Piper","doi":"10.1002/prp2.1115","DOIUrl":"https://doi.org/10.1002/prp2.1115","url":null,"abstract":"<p><p>Opioid overdose remains a problem in the United States despite pharmacotherapies, such as buprenorphine, in the treatment of opioid use disorder. This study characterized changes in buprenorphine use. Using the Drug Enforcement Administration's ARCOS, Medicaid, and Medicare claims databases, patterns in buprenorphine usage in the United States from 2018 to 2020 were analyzed by examining percentage changes in total grams distributed and changes in grams per 100 K people in year-to-year usage based on ZIP code and state levels. For ARCOS from 2018 to 2019 and 2019 to 2020, total buprenorphine distribution in grams increased by 16.2% and 12.6%, respectively. South Dakota showed the largest statewide percentage increase in both 2018-2019 (66.1%) and 2019-2020 (36.7%). From 2018 to 2019, the ZIP codes ND-577 (156.4%) and VA-222 (-82.1%) had the largest and smallest percentage changes, respectively. From 2019 to 2020, CA-932 (250.2%) and IL-603 (-36.8%) were the largest and smallest, respectively. In both 2018-2019 and 2019-2020, PA-191 had the second highest increase in grams per 100K while OH-452 was the only ZIP code to remain in the top three largest decreases in grams per 100K in both periods. Among Medicaid patients in 2018, there was a nearly 2000-fold difference in prescriptions per 100k Medicaid enrollees between Kentucky (12 075) and Nebraska (6). Among Medicare enrollees in 2018, family medicine physicians and other primary care providers were the top buprenorphine prescribers. This study not only identified overall increases in buprenorphine availability but also pronounced state-level differences. Such geographic analysis can be used to discern which public policies and regional factors impact buprenorphine access.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/78/c2/PRP2-11-e01115.PMC10364307.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10232926","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":"Could cannabinoids provide a new hope for ovarian cancer patients?","authors":"Rimanee Kaur,&nbsp;Farideh A Javid","doi":"10.1002/prp2.1122","DOIUrl":"https://doi.org/10.1002/prp2.1122","url":null,"abstract":"<p><p>It is known that gynecological cancers remain a worldwide problem and as shown by the statistics, there is a need for new gynecological cancer treatments. Cannabinoids, the pharmacologically active compounds of the Cannabis sativa plant, have been used for many centuries by individuals as a symptomatic treatment to alleviate pain, nausea, vomiting, and to help stimulate appetite. Research has revealed that cannabinoids also exert anti-cancer activity such as anti-proliferative and pro-apoptotic effects through a variety of mechanisms. There is significant value in the development of these compounds as anti-cancer therapies in clinical practice as they do not produce the typical toxic side effects that exist with conventional therapies and recent clinical trials have shown their great tolerability by patients at high doses. Cannabinoids can induce psychoactive effects that could limit their progression. Therefore, non-psychoactive cannabinoids are attracting pharmacological interest due to their inability to produce psychological effects. Recent studies have focussed on non-psychoactive cannabinoids in ovarian cancer and have revealed promising pre-clinical results that indicate that these compounds may have potential benefits in the treatment of these cancers. However, there are still unanswered questions and research gaps that need to be addressed. This review summarizes the current understanding of this topic and identifies the current gaps in knowledge that provide a useful direction for future work.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10391716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9922384","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":"Analysis of safety specifications in risk management plan at the time of drug approval and addition of clinically significant adverse reactions in the package insert post-approval in Japan.","authors":"Rieko Saito,&nbsp;Seiko Miyazaki","doi":"10.1002/prp2.1110","DOIUrl":"https://doi.org/10.1002/prp2.1110","url":null,"abstract":"<p><p>Recently, post-marketing safety measures have been considered critical in Japan due to the globalization of drug development and the introduction of new drug approval systems. Pharmacists are expected to play an active role in ensuring the safety of drugs post-approval. Utilizing risk management plans (RMPs) to ensure safety throughout the development and post-marketing phases is becoming even more critical. In this study, we examine the relationship between the safety specifications (SSs) in RMPs at the time of drug approval and the adverse reactions (ARs) added to the clinically significant adverse reactions (CSARs) section of the package inserts (PIs) post-approval to determine whether SSs constitute useful drug information for pharmacists. The analysis included new active ingredient-containing drugs approved in Japan from FY2013 to 2019. A 2 × 2 contingency table was created and analyzed using odds ratios (ORs) and Fisher's exact test. The OR was 14.22 (95% CI: 7.85-24.77; p < .001), which indicates a strong relationship between the ARs being SSs at the time of approval and being added to the PIs as CSARs post-approval. The positive predictive value that SSs at the time of approval were added as CSARs to the PIs post-approval was 7.1%. In addition, a similar relationship was observed with the \"approval in shorter-period drugs\" reviewed for approval based on a limited number of clinical trials. Therefore, SSs in RMPs are important drug information for pharmacists in Japan.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2f/dc/PRP2-11-e01110.PMC10293701.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9718840","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}