Pharmacology Research & Perspectives最新文献

{"title":"Plasma and urinary CP I and CP III concentrations in chimeric mice with human hepatocytes after rifampicin administration.","authors":"Yurina Shishido, Tomohiro Yoshida, Keiyu Oshida, Masashi Uchida","doi":"10.1002/prp2.70017","DOIUrl":"10.1002/prp2.70017","url":null,"abstract":"<p><p>The interest in transporter-mediated drug interactions has been increasing in the field of drug development. In this study, we measured the plasma and urinary concentrations of coproporphyrin (CP) I and CP III as endogenous substrates for organic anion-transporting polypeptide (OATP) using chimeric mice with human hepatocytes (PXB mice) and examined the influence of an OATP inhibitor, rifampicin (RIF). CP I and CP III were actively taken up intracellularly, and RIF inhibited the uptake in a concentration-dependent manner for both CP I and CP III in human hepatocytes (PXB-cells). Single doses of RIF at 10 and 30 mg/kg were orally or intravenously administered to PXB mice and wild-type ICR mice. Plasma concentrations (AUC_0-8h) of CP I increased in both mice. However, a marked increase in CP III was only observed in ICR mice, after intravenous administration of RIF at 30 mg/kg. The IC₅₀ values of RIF for intracellular CP I/III uptake and the unbound plasma concentrations of RIF suggested that the increase in plasma CP I is associated with the exposure of RIF to OATPs. The 24-h cumulative urinary excretions of CP I and CP III increased in both mice, but more markedly in PXB mice. Thus, RIF increased the plasma and urinary concentrations of CP I and CP III in the mice, as reported in humans, and CP I may be a more sensitive biomarker of OATP-mediated drug interactions in PXB mice.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 5","pages":"e70017"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293051","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":"Interaction of myricetin, ampelopsin (dihydromyricetin), and their sulfate metabolites with serum albumin, cytochrome P450 (CYP2C9, 2C19, and 3A4) enzymes, and organic anion-transporting polypeptides (OATP1B1 and OATP2B1).","authors":"Ágnes Dombi, Hana Kaci, Kateřina Valentová, Éva Bakos, Csilla Özvegy-Laczka, Miklós Poór","doi":"10.1002/prp2.70021","DOIUrl":"10.1002/prp2.70021","url":null,"abstract":"<p><p>Myricetin (MYR) and ampelopsin (AMP, or dihydromyricetin) are flavonoid aglycones found in certain plants and dietary supplements. During the presystemic biotransformation of flavonoids, mainly sulfate and glucuronide derivatives are produced, which are the dominant metabolites in the circulation. In this study, we tested the interactions of MYR, myricetin-3'-O-sulfate (M3'S), AMP, and ampelopsin-4'-O-sulfate (A4'S) with human serum albumin (HSA), cytochrome P450 enzymes (CYPs), and organic anion-transporting polypeptides (OATPs) using in vitro models, including the recently developed method for measuring flavonoid levels in living cells. M3'S and MYR bound to albumin with high affinity, and they showed moderate displacing effects versus the Site I marker warfarin. MYR, M3'S, AMP, and A4'S exerted no or only minor inhibitory effects on CYP2C9, CYP2C19, and CYP3A4 enzymes. M3'S and MYR caused considerable inhibitory actions on OATP1B1 at low micromolar concentrations (IC₅₀ = 1.7 and 6.4 μM, respectively), while even their nanomolar levels resulted in strong inhibitory effects on OATP2B1 (IC₅₀ = 0.3 and 0.4 μM, respectively). In addition, M3'S proved to be a substrate of OATP1B1 and OATP2B1. These results suggest that MYR-containing dietary supplements may affect the OATP-mediated transport of certain drugs, and OATPs are involved in the tissue uptake of M3'S.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 5","pages":"e70021"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11440035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351792","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":"Histamine H₁-receptor-mediated modulation of NMDA receptors signaling responses.","authors":"J-M Arrang, V Armand","doi":"10.1002/prp2.1216","DOIUrl":"https://doi.org/10.1002/prp2.1216","url":null,"abstract":"<p><p>This study attempted to clarify the role of histamine H₁ receptors in epilepsy by exploring the effects of agonists and inverse agonists on the rundown of the current induced by iterative applications of NMDA or GABA in primary neuronal culture. Mepyramine, a classical H₁-receptor antagonist/inverse agonist, increased the NMDA current by about 40% during the first minutes of recording. This effect was concentration-dependent, maximal at 10 nM, and mimicked by triprolidine, another antagonist/inverse agonist. No endogenous histamine was detected in the cultures by a selective immunoassay; both compounds were acting as inverse agonists. Indicating a high constitutive activity of the H₁ receptor in this system, histamine did not affect the NMDA rundown, including its settlement, but significantly reversed the effect of mepyramine. A similar pattern was obtained with 2,3 bromophenyl histamine, a selective H₁-receptor agonist. The initial increase induced by the two inverse agonists was followed by the same rundown as in controls. H₁- and NMDA receptors are colocalized in most cultured neuronal cells. Mepyramine and histamine did not affect the GABA rundown. Our findings suggest an interaction between H₁- and NMDA receptors. Inactivation of the H₁-receptor by its inverse agonists delays the settlement of the NMDA rundown, which may underlie their proconvulsant effect reported in clinics. Therefore, H₁-receptor constitutive activity and the effect of histamine revealed in its absence, tend to facilitate the initiation of the rundown, which is consistent with the anticonvulsant properties of histamine via activation of H₁-receptors reported in many studies.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 5","pages":"e1216"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392404","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 pharmacokinetic modeling of vedolizumab for graft-versus-host disease prophylaxis in adults with allogeneic hematopoietic stem cell transplant.","authors":"Timothy Waterhouse, Kyle Baron, Westley Eure, Chunlin Chen, Nathanael L Dirks, Johan Jansson, Mona Akbari, Shailly Mehrotra","doi":"10.1002/prp2.1257","DOIUrl":"10.1002/prp2.1257","url":null,"abstract":"<p><p>We aimed to characterize the population pharmacokinetics (PK) of vedolizumab for acute graft-versus-host disease prophylaxis in adults undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) and assess potential clinically relevant covariates. Dosing, patient characteristics, and PK from a phase 1b, open-label, dose-finding study of vedolizumab 75 mg initial dose escalated to 300 mg and a phase 3 study of vedolizumab 300 mg in patients receiving allo-HSCT were analyzed using a two-compartment population PK model with linear elimination. Covariates included age, race, weight, sex, albumin, lymphocyte count, GvHD type, and concomitant medications. Weight, albumin, and lymphocyte count were time-varying covariates. Model selection was driven by goodness-of-fit criteria, precision of parameter estimates, and visual predictive checks. In 193 patients undergoing allo-HSCT, vedolizumab PK were well described by a two-compartment, linear PK model. Using reference covariate values, final parameter estimates (95% confidence intervals [CI]) were: clearance, 0.148 (0.136, 0.162) L/day; central volume of distribution, 3.12 (3.03, 3.21) L; intercompartmental clearance, 0.500 (0.408, 0.612) L/day; and peripheral volume of distribution, 3.95 (3.52, 4.44) L. Weight and albumin were the most important predictors of vedolizumab PK, with clearance decreasing by ≈20% for low body weight/high albumin and increasing by ≈30% for high body weight/low albumin. There was an inverse relationship between vedolizumab clearance and age, but no detectable effect for lymphocyte count or GvHD type. Post hoc analyses did not detect any relationship between vedolizumab PK and concomitant medications. In summary, the covariates studied did not have a clinically meaningful effect on the PK of vedolizumab.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 5","pages":"e1257"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11374527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133446","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":"Nutritional strategies for improving sarcopenia outcomes in older adults: A narrative review.","authors":"Beatriz R Goes-Santos, Brian P Carson, Guilherme Wesley Peixoto da Fonseca, Stephan von Haehling","doi":"10.1002/prp2.70019","DOIUrl":"https://doi.org/10.1002/prp2.70019","url":null,"abstract":"<p><p>Sarcopenia is characterized by a decline in muscle strength, generalized loss of skeletal muscle mass, and impaired physical performance, which are common outcomes used to screen, diagnose, and determine severity of sarcopenia in older adults. These outcomes are associated with poor quality of life, increased risk of falls, hospitalization, and mortality in this population. The development of sarcopenia is underpinned by aging, but other factors can lead to sarcopenia, such as chronic diseases, physical inactivity, inadequate dietary energy intake, and reduced protein intake (nutrition-related sarcopenia), leading to an imbalance between muscle protein synthesis and muscle protein breakdown. Protein digestion and absorption are also modified with age, as well as the reduced capacity of metabolizing protein, hindering older adults from achieving ideal protein consumption (i.e., 1-1.5 g/kg/day). Nutritional supplement strategies, like animal (i.e., whey protein) and plant-based protein, leucine, and creatine have been shown to play a significant role in improving outcomes related to sarcopenia. However, the impact of other supplements (e.g., branched-chain amino acids, isolated amino acids, and omega-3) on sarcopenia and related outcomes remain unclear. This narrative review will discuss the evidence of the impact of these nutritional strategies on sarcopenia outcomes in older adults.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 5","pages":"e70019"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472218","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":"Nicotine addiction and the influence of life adversity and acute stress on PYY: Prediction of early smoking relapse.","authors":"Amanda A Miller, Motohiro Nakajima, Briana N DeAngelis, Dorothy K Hatsukami, Mustafa al'Absi","doi":"10.1002/prp2.70016","DOIUrl":"10.1002/prp2.70016","url":null,"abstract":"<p><p>Early life adversity (ELA) is associated with earlier initiation and maintenance of tobacco smoking and with a greater risk of subsequent relapse. There is growing evidence that appetite hormones, including peptide YY (PYY), which modulates craving and satiety responses, play a role in stress and addiction processes. This study employed a quasi-experimental design to examine the association between ELA and circulating PYY stress responses in smokers and nonsmokers (N = 152, ages 19-73 years) to examine the effects of nicotine addiction. Smokers initiated a quit attempt as part of the study and were classified as either abstinent smokers or relapsed smokers based on their nicotine use during the follow-up period. PYY levels were measured at five timepoints during three lab sessions and compared between nonsmokers and the two smoking groups (abstainers, relapsers): while smokers were using nicotine ad libitum, 24 h after smokers initiated a quit attempt, and 4 weeks after smokers initiated a quit attempt. Multivariate analyses showed the main effects of time on PYY, which decreased over time within each session. The main effects of ELA during the first (ad libitum smoking) and second (24-h post-cessation for smokers) sessions indicated that experiencing ELA was associated with lower PYY. No systematic effect of nicotine addiction or relapse was observed in this study. These findings suggest that adults with higher ELA may experience lower PYY. Additional research is needed to further explore the role of PYY in stress and addiction processes.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 5","pages":"e70016"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11420658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308349","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 pharmacodynamics of the factor XIa-inhibiting antibody osocimab in healthy male East Asian volunteers: Results from two phase 1 studies.","authors":"Zhili Dong, Kensei Hashizume, Frauke Friedrichs, Pei Liu, Toshiaki Tanaka, Yuqin Liao","doi":"10.1002/prp2.70012","DOIUrl":"10.1002/prp2.70012","url":null,"abstract":"<p><p>The pharmacokinetics, pharmacodynamics, immunogenicity, and safety of osocimab single doses in healthy Chinese and Japanese volunteers over 149 days were evaluated. Two phase 1 single-blinded, placebo-controlled studies with 27 Japanese and 50 Chinese participants were conducted. Osocimab was investigated with IV doses of 0.3, 1.25, and 2.5 mg/kg (Chinese study) and 0.3, 1.25, and 5.0 mg/kg (Japanese study), as well as SC doses of 3.0 and 6.0 mg/kg (Chinese study) and 6.0 mg/kg (Japanese study). The maximum plasma concentration was reached 1-3 h and 4-6 days after IV and SC administration, respectively. Osocimab exhibited a deviation from dose-proportional pharmacokinetics for AUC but not C_max; higher doses had higher apparent clearance and disproportionately lower total exposure. A slightly lower exposure was observed in Japanese compared with Chinese volunteers after IV administration; conversely, relatively higher exposure in Japanese volunteers with SC dosing was identified. Osocimab was associated with a dose-dependent increase in activated partial thromboplastin time (aPTT). Maximal aPTT prolongations were observed 1-4 h and 2-6 days after IV and SC administration, respectively. Anti-drug antibodies of low titer were detected in 1/9 (11.1%) Japanese volunteers administered placebo and 26/40 (65.0%) Chinese volunteers administered osocimab. Adverse events were reported in 8/18 (44.4%) Japanese and 28/40 (70.0%) Chinese volunteers who received osocimab, as well as in 1/9 (11.1%) Japanese and 6/10 (60.0%) Chinese volunteers who received placebo. In conclusion, data did not suggest a clear dose-proportionality for osocimab within the investigated dose range. The effect of osocimab on aPTT was expected per its mechanism of action. Osocimab was generally well tolerated.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 5","pages":"e70012"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293050","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":"Effect of mitochondrial coenzyme-Q10 precursor solanesol in gentamicin-induced experimental nephrotoxicity: Evidence from restoration of ETC-complexes and histopathological alterations.","authors":"Minakshi Sangwan, Hema Chaudhary, Sidharth Mehan, Zuber Khan, Ammar A Bahauddin, Bandar D Alrehaili, Hossein M Elbadawy, Mohannad A Almikhlafi, Acharan S Narula, Reni Kalfin, Hanna Wanas","doi":"10.1002/prp2.70022","DOIUrl":"10.1002/prp2.70022","url":null,"abstract":"<p><p>Nephrotoxicity occurs when the body is exposed to certain drugs or toxins. When kidney damage occurs, the kidney fails to eliminate excess urine and waste. Solanesol (C45H74O) is a tri-sesquiterpenoid alcohol first isolated from tobacco, and it is widely distributed in plants of the Solanaceae family. Solanesol (SNL) is an intermediate in the synthesis of coenzyme Q10 (CoQ10), an antioxidant which protects nerve cells. This study investigated the protective effect of SNL at doses of 30 and 60 mg/kg in gentamicin-induced nephrotoxicity in Wistar albino rats. Animals were distributed into six groups and administered 100 mg/kg gentamicin-intraperitoneal injection for 14 days. Biochemical assessments were performed on kidney homogenate, blood, and serum. Treatment with SNL was shown as lower serum levels of creatinine, blood urea nitrogen (BUN), thiobarbituric acid reactive substances (TBARS), and Tumor necrosis factor alpha)TNF-α ((p < .001). It also restored reduced glutathione (GSH) and mitochondrial complex enzymatic activity as protective measures against gentamicin-induced nephrotoxicity. SNL were shown to reduce inflammation and oxidative stress markers (p < .001). Histological findings furtherly augmented the protective effects of SNL. Long-term SNL therapy also restored mitochondrial electron transport chain complex enzymes, such as complex-I (p < .001). In conclusion, these findings suggest that SNL can represent a protective therapeutic option for drug-induced nephrotoxicity, a long-term adverse effect of aminoglycoside antibiotics such as gentamicin.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 5","pages":"e70022"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366185","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":"Risks of oral anticoagulants: Analysis of adverse drug reactions reported to the Portuguese National Pharmacovigilance System","authors":"Ana Sofia Martins, Cristina Monteiro, Ana Paula Duarte","doi":"10.1002/prp2.1235","DOIUrl":"https://doi.org/10.1002/prp2.1235","url":null,"abstract":"Cardiovascular diseases are the leading cause of death globally, making the use of oral anticoagulants for prevention increasingly important. Historically, warfarin has played a significant role in this context. In recent years, introduction of new oral anticoagulants, such as rivaroxaban, apixaban, dabigatran, and edoxaban, has been seen. This study evaluates the risk associated with the use of oral anticoagulants by analyzing spontaneous adverse drug reactions reported to the Portuguese Pharmacovigilance System from 2012 to 2021. The study includes 951 adverse drug reactions reports, with the majority (<jats:italic>n</jats:italic> = 770; 80.97%) classified as serious. Of the 770 serious adverse drug reactions reports, the most commonly reported seriousness criterion was “Clinically Important” (<jats:italic>n</jats:italic> = 350; 45.45%). In terms of demographics, there was a higher reporting rate among the elderly population, with a greater prevalence of females. The System Organ Class group with the highest number of adverse drug reactions was “Gastrointestinal disorders,” with the most commonly reported Preferred Term being “Gastrointestinal hemorrhage,” and dabigatran was the most frequently reported drug. In summary, oral anticoagulants have adverse drug reactions that require continuous monitoring. Accurate identification and monitorization of adverse drug reactions is an important starting point to improve drug safety in population.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"33 1","pages":"e1235"},"PeriodicalIF":2.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the quality of multiple‐choice question pilot database: A global educator‐created tool for concept‐based pharmacology learning","authors":"Adeladlew Kassie Netere, Tony Hughes, Anna‐Marie Babey, Martin Hawes, Janet Mifsud, John P. Kelly, Willmann Liang, Mark Hernandez, Kelly Karpa, Hesham Al‐Sallami, Lynette B. Fernandes, Patrik Aronsson, Carolina Restini, Fabiana Caetano Crowley, Elvan Djouma, Tina Hinton, Johnson J. Liu, Fatima Mraiche, Paul J. White","doi":"10.1002/prp2.70004","DOIUrl":"https://doi.org/10.1002/prp2.70004","url":null,"abstract":"The Core Concepts of Pharmacology (CCP) initiative is developing educational resources to transform pharmacology education into a concept‐based approach. This study evaluated the quality of global educator‐created MCQs in generating items for the pharmacology concept inventory (PCI) instrument and developed as a resource for learning pharmacology fundamental concepts. A panel of 22 global pharmacology experts recruited from the CCP initiative research team participated in the MCQ pilot database design and evaluation. The quality analysis framework of the MCQs in the pilot database included four assessment tools: item writing guidelines (IWGs), Bloom's taxonomy, the CCP, and the MCQ design format. A two‐phase evaluation process was involved, including inter‐rater agreement on item quality, followed by resolving conflicts that occurred in quality assessment. The chi‐square (<jats:italic>χ</jats:italic><jats:sup>2</jats:sup>) test of independence and Cramer's V correlation tests were utilized to measure the relationship among quality assessment attributes. About 200 MCQs were gathered and 98% underwent expert evaluation. Nearly 80% addressed one or more CCP, with 52% designed using a context‐dependent format. However, only 40% addressed higher levels of Bloom's cognitive domain and 10% adhered to all IWGs. A strong positive correlation was observed between the context‐based item format and its effectiveness in assessing the higher cognitive domain, the main CCP and improved IWGs adherence. Context‐based item construction can assess the higher cognitive skills and fundamental pharmacology concepts, showing potential for rigorous PCI development. The pilot database will store items to create the PCI, aiding the development of a concept‐based pharmacology curriculum.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"101 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265087","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}