Pharmacology Research & Perspectives最新文献

{"title":"The Absorption, Distribution, Metabolism, and Excretion of Binimetinib Following a Single Oral Dose of [¹⁴C]Binimetinib 45 mg in Healthy Male Participants.","authors":"Dustin Huynh, Erik Hahn, Micaela B Reddy, Renae Chavira, Lance Wollenberg","doi":"10.1002/prp2.70061","DOIUrl":"10.1002/prp2.70061","url":null,"abstract":"<p><p>Binimetinib is a MEK1/2 inhibitor particularly active in cells harboring activating mutations in the MAP kinase pathway, especially in BRAF and NRAS. Binimetinib, in combination with encorafenib, has received marketing approval in several jurisdictions for the treatment of patients with BRAF V600E or V600K mutant melanoma. The absorption, distribution, metabolism, and excretion of binimetinib were evaluated by administering a carbon 14-labeled binimetinib 45 mg dose (containing 40 μCi of radiolabeled material) to 6 healthy male participants. A total of 62.3% of the radioactivity was eliminated in the feces, while 31.4% was eliminated in the urine. The overall recovery of radioactivity in the excreta for all 6 participants was 93.6% (3.27%), indicating that good mass balance was achieved. The total percentage of the dose in the excreta of all metabolites containing the N-demethylation clearance of binimetinib by CYP1A2 and CYP2C19 was approximately 17.8%. The contribution of direct glucuronidation to the clearance of binimetinib was estimated to be 61.2% and represented the majority of the clearance. Additionally, excretion of unchanged binimetinib into the urine was estimated to have contributed 6.9% to the overall clearance. Based on study results, binimetinib is at least ≈ 50% absorbed, but based on its PK properties and because its glucuronide conjugates are unstable in the GI tract, absorption is thought to be significantly higher.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 1","pages":"e70061"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Clinical Practice-Based Comparison of Conventional and Individualized Dosing Strategies for Therapeutic Enoxaparin.","authors":"Anthony Damiani, Viviane De Menezes Caceres, Greg Roberts, Jessica Coddo, Nicholas Scarfo, Desmond B Willliams, Vinosshini Tharmathurai, Rami Tadros, Stephen Fitzgerald, Alice O'Connell, Amrit Kaur Sandhu, Andrew Vanlint, Arduino A Mangoni, Dirk Hofmann, Hosam Bony, Jeff Faunt, Jir Ping Boey, Nicholas Farinola, Rachel Wells, Stephen Hedger, Udul Hewage, Yogesh Sharma, Zuhair Jabbar, Josephine Thomas, Katerina Flabouris, Toby Gilbert, Campbell Thompson, Patrick Russell","doi":"10.1002/prp2.70039","DOIUrl":"10.1002/prp2.70039","url":null,"abstract":"<p><p>To understand differences in anti-factor-Xa levels produced by two different dosing strategies (conventional and individualized) for therapeutic enoxaparin in a cohort of hospital inpatients. A multicenter, retrospective cohort study over a two- and a half-year period for inpatients with stable renal function and on therapeutic enoxaparin. Anti-factor-Xa levels were taken 3-5 h after enoxaparin administration and a minimum of 48 h of dosing. The final analysis included 278 patients from five hospitals: conventional dosing was used for 141, while 137 were given an unconventional dose, that is, individualized for their renal function and weight. Out-of-range levels were frequent (35% to 40% of all inpatients). After adjustment for age, renal function, and body mass index (BMI), the conventional group was more likely to experience above-range levels (> 1.0 IU/mL; OR 2.50 [95% CI 1.38-4.56], p < 0.003) than the individualized group. Individualized dosing was independently associated with higher odds of a below-range anti-Xa level (< 0.5 IU/mL) compared to conventional dosing (OR 2.27 [95% CI 1.07-4.76], p = 0.03). Within the conventional group, above-range levels were significantly and independently associated with decreasing renal function (OR 0.97, 95% CI 0.96-0.99, p = 0.004) and with increasing BMI (OR 1.06, 95% CI 1.01-1.10, p = 0.02). No such associations were seen with an individualized approach. Clinical event rates were low and not different between groups (p > 0.24). Conventional therapeutic dosing of enoxaparin exposed people with obesity or renal impairment to more frequent above-range anti-factor-Xa levels; individualizing the dose could improve this but might expose people to subtherapeutic levels. More research is needed.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 1","pages":"e70039"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033061","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":"Transfer of the Oral Gonadotropin-Releasing Hormone Receptor Antagonist Relugolix Into Breast Milk of Healthy Lactating Women.","authors":"Darin B Brimhall, Yu-Luan Chen, Sarah Lee, Kazumasa Yoshida, Mike Ufer","doi":"10.1002/prp2.70067","DOIUrl":"10.1002/prp2.70067","url":null,"abstract":"<p><p>Relugolix is an oral gonadotropin-releasing hormone receptor antagonist that suppresses sex steroid hormones and is approved as monotherapy for prostate cancer and as a fixed-dose combination with estradiol/norethindrone for the treatment of endometriosis and uterine fibroids. The aim of this postmarketing study was to determine the pharmacokinetics and quantify the amount of relugolix excreted into breast milk of healthy lactating women. Following a single, oral dose of 40 mg relugolix, breast milk was sampled over 120 h. Pharmacokinetic parameters were determined, including the cumulative amount of relugolix excreted into breast milk to derive the total infant dose. The safety and tolerability of relugolix were also assessed. Eight healthy lactating women were enrolled and completed the study per protocol. Relugolix was safe and well tolerated based on adverse events and other safety data. It was excreted into breast milk with a median time to peak concentration (t_max) of 5.81 h and a geometric mean peak concentration (C_max) of 15.7 ng/mL, similar to corresponding plasma data from previous clinical studies. The mean cumulative amount of relugolix excreted was 0.0051 mg over 24 h and 0.0067 mg over 120 h, corresponding to 0.0128% and 0.0167% of the maternal dose, respectively. The body weight-adjusted relative daily infant dose of approximately 0.25% suggests a 400-fold lower newborn than maternal relugolix exposure. Relevant effects of relugolix on the breastfed child appear unlikely given its limited excretion into breast milk of lactating women but cannot be fully excluded in the absence of infant safety data.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 1","pages":"e70067"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066960","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":"β2-Adrenergic Receptor Agonist Clenbuterol Protects Against Acute Ischemia/Reperfusion-Induced Arrhythmia by Regulation of Akt/eNOS/NO/Cx43 Signaling Pathway.","authors":"Jing Fu, Li Liu, Qin Fu, Xiaoman Zeng, Xiaoyan Yang","doi":"10.1002/prp2.70070","DOIUrl":"10.1002/prp2.70070","url":null,"abstract":"<p><p>Ventricular arrhythmias induced by ischemia/reperfusion injury limits the therapeutic effect of early reperfusion therapy for acute myocardial infarction. This study investigated the protective effects of the β2-adrenergic receptor (β2-AR) agonist clenbuterol against ischemia/reperfusion-induced arrhythmias and the underlying mechanism. Anesthetized rats were subjected to 10-min left coronary artery occlusion and 10-min reperfusion in vivo. Langendorff-perfused mice hearts were exposed to 10-min global ischemia and 10-min reperfusion. Arrhythmic events were recorded during early reperfusion. Hearts were collected for measuring nitric oxide (NO) concentration and immunoblotting of Connexin 43 (Cx43), endothelial nitric oxide synthase (eNOS), and protein kinase B (Akt). After the ischemia/reperfusion injury in anesthesia rats, clenbuterol markedly reduced the duration and incidence of ventricular tachycardia and ventricular fibrillation, and arrhythmia score, which was abrogated by selective β2-AR antagonist or Cx43 inhibitor. Furthermore, a marked increase in dephosphorylated Cx43 expression and a decrease in the ratio of phosphorylated Cx43 to total Cx43 were observed after the ischemia/reperfusion injury. Mechanistically, clenbuterol increased the phosphorylation of e-NOS and NO concentration, while L-NAME abolished Cx43 phosphorylation and the protective effect of clenbuterol. Clenbuterol also promoted Akt phosphorylation, and blockade of Akt inhibited eNOS phosphorylation and NO production, as well as Cx43 phosphorylation and protective effect of clenbuterol. The present study elucidates that β2-AR stimulation activates the Akt/eNOS signaling pathway, augments NO bioavailability, maintains Cx43 phosphorylation, and prevents Cx43 remodeling, ultimately attenuating arrhythmia induced by ischemia/reperfusion.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 1","pages":"e70070"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053096","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":"Non-Linear Dose-Response Relationship for Metformin in Japanese Patients With Type 2 Diabetes: Analysis of Irregular Longitudinal Data by Interpretable Machine Learning Models.","authors":"Hayato Akimoto, Takuya Nagashima, Kimino Minagawa, Takashi Hayakawa, Yasuo Takahashi, Satoshi Asai","doi":"10.1002/prp2.70055","DOIUrl":"10.1002/prp2.70055","url":null,"abstract":"<p><p>The dose-response relationship between metformin and change in hemoglobin A1c (HbA1c) shows a maximum at 1500-2000 mg/day in patients with type 2 diabetes (T2D) in the U.S. In Japan, there is little evidence on the HbA1c-lowering effect of high-dose metformin because the maintenance and maximum doses of metformin were raised in 2010. The aim of this study was to investigate whether there is saturation of the dose-response relationship for metformin in Japanese T2D patients. Longitudinal clinical information of T2D patients was extracted from electronic medical records. Supervised machine learning models with random effect were constructed to predict change in HbA1c: generalized linear mixed-effects models (GLMM) with/without a feature selection and combining tree-boosting with Gaussian process and mixed-effects models (GPBoost). GPBoost was interpreted by SHapley Additive exPlanations (SHAP) and partial dependence. GPBoost had better predictive performance than GLMM with/without feature selection: root mean square error was 0.602 (95%CI 0.523-0.684), 0.698 (0.629-0.774) and 0.678 (0.609-0.753), respectively. Interpretation of GPBoost by SHAP and partial dependence suggested that the relationship between the daily dose of metformin and change in HbA1c is non-linear rather than linear, and the HbA1c-lowering effect of metformin reaches a maximum at 1500 mg/day. Interpretation of GPBoost, a non-linear supervised machine-learning algorithm, suggests that there is saturation of the dose-response relationship of metformin in Japanese patients with T2D. This finding may be useful for decision-making in pharmacotherapy for T2D.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 1","pages":"e70055"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11797302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255279","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":"Melatonin: A Review of the Evidence for Use in Hospital Settings.","authors":"Josephine A Adattini, Carly Wills, Jennifer H Martin","doi":"10.1002/prp2.70059","DOIUrl":"10.1002/prp2.70059","url":null,"abstract":"<p><p>New onset insomnia is often experienced by patients during hospitalization due to environmental disruptions, pain and increased patient care activities. Patient distress arising from poor sleep quality and quantity often results in the prescribing of hypnotics. Melatonin use in hospital settings is common and is increasingly used for off label indications including primary insomnia in those aged < 55 years, prevention of delirium and to facilitate benzodiazepine discontinuation. A literature review was conducted to evaluate the efficacy, effectiveness, safety, tolerability, and cost-effectiveness of melatonin for various off-label indications in inpatient hospital settings. The review found limited high quality evidence demonstrating a clinically meaningful benefit from melatonin in improving sleep, delirium, or facilitating benzodiazepine discontinuation in the inpatient setting. Study findings were inconsistent, and those that did show statistical improvement were of uncertain clinical benefit. The review also found a paucity of data on the safety of melatonin when used in hospitalized patients, and no evidence to support cost-effectiveness. Non-pharmacological interventions are recommended as first-line treatment of insomnia and for the prevention of delirium in inpatient settings. The use of interventions without evidence for efficacy or effectiveness is contrary to the quality use of medicines principles in Australia's National Medicines Policy. Context-specific evidence on the efficacy and effectiveness of a medicine should guide clinician decision-making and prescribing, to improve the quality use of medicines.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 1","pages":"e70059"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009874","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":"Edaravone is a Therapeutic Candidate for Doxorubicin-Induced Cardiomyopathy by Activating the Nrf2 Pathway.","authors":"Naoki Yoshikawa, Naoto Hirata, Yuichiro Kurone, Sadahiko Shimoeda","doi":"10.1002/prp2.70066","DOIUrl":"10.1002/prp2.70066","url":null,"abstract":"<p><p>Doxorubicin (DOXO) has long been used clinically and remains a key drug in cancer therapy. DOXO-induced cardiomyopathy (DICM) is a chronic and fatal complication that severely limits the use of DOXO. However, there are very few therapeutic agents for DICM, and there is an urgent need to identify those that can be used for a larger number of patients. The most likely pathogenic mechanism of DICM is the involvement of reactive oxygen species (ROS) and promotion of cell death. In this study, we investigated the efficacy and mechanism of action of edaravone (EDA), a known radical scavenger in DICM. Two methods of EDA administration were employed: daily and weekly. Our results showed that the daily administration group had prolonged survival periods and preserved the left ventricular ejection fraction in DICM mice. In contrast, in the weekly treatment group, slight improvements were observed in these indicators compared with those in DICM mice; however, none of them were statistically significant. These results show that the daily administration group had a higher efficacy than the weekly administration group. Gene-expression results showed that Nrf2 and its related genes were upregulated in the daily group but not in the weekly group. Based on these results, we hypothesized that the Sirt1/Nrf2/HO-1 and ABCB4 pathways were involved in EDA. However, there is limited evidence that EDA is effective against DICM. The findings obtained herein bolster the evidence in DICM by demonstrating prolonged survival and continued preservation of cardiac function and proposing a possible mechanism.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 1","pages":"e70066"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047364","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":"BCyrius: An Upgraded Version of Cyrius for Accurate CYP2D6 Genotyping From Short-Read Sequencing Data.","authors":"Andreas Halman, Rachel Conyers","doi":"10.1002/prp2.70065","DOIUrl":"10.1002/prp2.70065","url":null,"abstract":"<p><p>Pharmacogenomics is a field of personalized medicine that aims to tailor drug dosing based on the genetics of an individual. The polymorphic and complex CYP2D6 gene is important to analyze because of its role in the metabolism of approximately a quarter of all drugs. Several bioinformatic tools have been developed to genotype CYP2D6 from short-read sequencing data. Among these, Cyrius, a tool specifically designed for CYP2D6 genotyping, has demonstrated high performance across various datasets. However, Cyrius has not been updated in the past 3 years, during which dozens of new star alleles have been identified and some previously defined ones revised. In this work, we simulated all known CYP2D6 haplotypes to assess the ability of Cyrius to identify them. In that dataset, Cyrius was unable to call or misidentified 50 of 360 samples. Given the importance of providing an up-to-date tool, particularly in clinical settings, we present an upgraded version of the tool, named BCyrius, which includes all the missing star alleles as well as revisions to the previously listed ones. BCyrius successfully identified 100% of the currently defined minor star alleles, higher than Cyrius (85.6%) and the two other tested tools, Aldy and StellarPGx, which identified 92.2% and 87.8%, respectively. BCyrius also demonstrated slightly improved performance on a dataset of real biological samples, resulting in a higher call rate while maintaining similar accuracy with Cyrius. In addition to providing genotyping results, BCyrius also reports the predicted phenotype, along with information for each detected haplotype, including population frequencies.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 1","pages":"e70065"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123398","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":"Phase I Study of the Safety, Tolerability, and Pharmacokinetics of Inhaled Voriconazole in Healthy Volunteers and Subjects With Stable Asthma.","authors":"Giovanni Caponetti, Federica Sala, Antonio Cervetti, Daniele Colombo, Elena Tiberio, Dave Singh","doi":"10.1002/prp2.70064","DOIUrl":"https://doi.org/10.1002/prp2.70064","url":null,"abstract":"<p><p>The aim of this study was to evaluate safety, tolerability, and pharmacokinetics (PK) of single and multiple doses of a novel inhaled formulation of voriconazole (ZP-059). In the single ascending dose part, 4 cohorts of 6 healthy subjects received one dose of inhaled voriconazole (5-40 mg). In the multiple ascending dose part, 3 cohorts of 6 subjects with mild asthma received voriconazole 10 mg twice daily [BID], 20 mg BID or 40 mg once daily. In the 2-period crossover part, 16 subjects with mild to moderate asthma each received one dose of inhaled voriconazole 20 mg and one dose of oral voriconazole 200 mg. A bioanalytical method was developed and validated to simultaneously determine concentrations of voriconazole and its metabolite N-oxide voriconazole in serum and sputum. Inhaled voriconazole was well tolerated with no treatment emergent adverse events (TEAEs) leading to treatment discontinuation. The PK profile of inhaled voriconazole showed rapid absorption, apparent greater than proportional increase in exposure with increasing dose, a consistent half-life across dosing, and large clearance and volume of distribution. Following repeat administration limited accumulation was observed. Systemic exposure following inhaled voriconazole was much lower than following oral voriconazole. Serum data confirmed that voriconazole was extensively metabolized also when administered by inhalation. Sputum data following inhaled voriconazole were limited but demonstrated increasing exposure with increasing dose. The current study shows the newly developed dry powder inhaled formulation of voriconazole to be safe and well tolerated, providing a possible improved treatment approach for patients affected by allergic bronchopulmonary aspergillosis. Trial Registration: ClinicalTrials.gov ID: NCT04229303.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 1","pages":"e70064"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364462","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":"Addressing Ethnicity in the Design and Evaluation of an Educational Intervention on Interindividual Variation in Pharmacokinetics.","authors":"Jennifer A Koenig, Olusola Olafuyi, Rakesh Patel","doi":"10.1002/prp2.70073","DOIUrl":"10.1002/prp2.70073","url":null,"abstract":"<p><p>Interindividual variation in pharmacokinetics can occur due to diet, environmental or lifestyle factors, underlying pathology, and gene variants, typically single nucleotide polymorphisms (SNPs). Genetic mechanisms have received the most attention in research and education about ethnic differences in pharmacokinetics. Making this connection between genetics and ethnicity is problematic because it could reinforce the erroneous idea that there is a biological basis to ethnicity. The aim of this work was to design an educational intervention about interindividual variation in pharmacokinetics, explore how students perceive ethnicity and genetic differences prior to the educational intervention, and then assess the impact of the intervention and whether it could influence any misconceptions students might have about ethnicity and genetic similarity. Through the use of questionnaires and focus groups, we found that students typically refer to ethnicity to mean culture and place of origin, whereas in the pharmacological literature, ethnicity is synonymous with racial groups, that is, Black, White, and Asian. Prior to the educational intervention, students tended to expect a genetic mechanism for ethnic differences in drug metabolism and this was reduced after the intervention when a range of other nongenetic mechanisms were presented for interindividual variation. However, students' views about possible underlying mechanisms for ethnic differences in hypertension and about ethnicity more generally were unaffected by the intervention. This highlights the importance of reevaluating the way ethnicity is presented across the medical and medical sciences curriculums to be clear that ethnicity is socially constructed and avoid implying a biological basis.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 1","pages":"e70073"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11800234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256323","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}