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Part 2: Drug Interactions Involving Cannabis Products in Persons Aged 18 and Over: A Summary of Published Case Reports and Analysis of the FDA Adverse Event Reporting System. 第2部分:18岁及以上人群中涉及大麻产品的药物相互作用:已发表病例报告总结和FDA不良事件报告系统分析。
IF 2.9 4区 医学
Pharmacology Research & Perspectives Pub Date : 2025-02-01 DOI: 10.1002/prp2.70047
Maryann R Chapin, Sandra L Kane-Gill, Xiaotong Li, Kojo Abanyie, Sanya B Taneja, Susan Egbert, Mary F Paine, Richard D Boyce
{"title":"Part 2: Drug Interactions Involving Cannabis Products in Persons Aged 18 and Over: A Summary of Published Case Reports and Analysis of the FDA Adverse Event Reporting System.","authors":"Maryann R Chapin, Sandra L Kane-Gill, Xiaotong Li, Kojo Abanyie, Sanya B Taneja, Susan Egbert, Mary F Paine, Richard D Boyce","doi":"10.1002/prp2.70047","DOIUrl":"10.1002/prp2.70047","url":null,"abstract":"<p><p>The increasing utilization of cannabis products combined with lack of data regarding potential cannabis-prescription drug interactions is concerning. This study aimed to review published case reports and FDA Adverse Event Reporting System (FAERS) spontaneous reports to assess cannabis-drug interactions in persons aged 18 and over. A literature search identified 20 case reports that were each assessed for drug interaction causality using the Drug Interaction Probability Scale. Data collected from the FAERS revealed a greater proportion of reports mentioning serious outcomes, including death, when cannabis was used concomitantly with controlled substances compared to noncontrolled substances. Fisher's exact test showed a statistically significant difference between the controlled and noncontrolled groups (p = 0.043). Overall, these findings emphasize the need for additional research and vigilant monitoring of cannabis use when combined with other medications.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 1","pages":"e70047"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885387","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
A549 Alveolar Carcinoma Spheroids as a Cytotoxicity Platform for Carboxyl- and Amine-Polyethylene Glycol Gold Nanoparticles. 羧基和胺-聚乙二醇金纳米颗粒作为肺泡癌球体的细胞毒性平台。
IF 2.9 4区 医学
Pharmacology Research & Perspectives Pub Date : 2025-02-01 DOI: 10.1002/prp2.70051
Melissa Petzer, Seth-Frerich Fobian, Mary Gulumian, Vanessa Steenkamp, Werner Cordier
{"title":"A549 Alveolar Carcinoma Spheroids as a Cytotoxicity Platform for Carboxyl- and Amine-Polyethylene Glycol Gold Nanoparticles.","authors":"Melissa Petzer, Seth-Frerich Fobian, Mary Gulumian, Vanessa Steenkamp, Werner Cordier","doi":"10.1002/prp2.70051","DOIUrl":"10.1002/prp2.70051","url":null,"abstract":"<p><p>Gold nanoparticles (AuNPs) present with unique physicochemical features and potential for functionalization as anticancer agents. Three-dimensional spheroid models can be used to afford greater tissue representation due to their heterogeneous phenotype and complex molecular architecture. This study developed an A549 alveolar carcinoma spheroid model for cytotoxicity assessment and mechanistic evaluation of functionalized AuNPs. A549 spheroids were generated using an agarose micro-mold and were characterized (morphology, acid phosphatase activity, protein content) over 21 culturing days. The 72-h cytotoxicity of carboxyl-polyethylene glycol- (PCOOH-) and amine-polyethylene glycol- (PNH<sub>2</sub>-) functionalized AuNPs against Day 7 spheroids was assessed by determining spheroid morphology, acid phosphatase activity, protein content, caspase-3/7 activity, and cell cycle kinetics. Spheroids remained stable over the experimental period. Although the A549 spheroids' volume increased while remaining viable over the culturing period, structural integrity decreased from Day 14 onwards. The PCOOH-AuNPs lacked cytotoxicity at a maximum concentration of 1.2 × 10<sup>12</sup> nanoparticles/mL with no prominent alteration to the cellular processes investigated, while the PNH<sub>2</sub>-AuNPs (at a maximum of 4.5 × 10<sup>12</sup> nanoparticles/mL) displayed dose- and time-dependent cytotoxicity with associated loss of spheroid compactness, debris formation, DNA fragmentation, and a 75% reduction in acid phosphatase activity. Differentiation between cytotoxic and non-cytotoxic AuNPs was achieved, with preliminary elucidation of cytotoxicity endpoints. The PNH<sub>2</sub>-AuNPs promote cytotoxicity by modulating cellular kinetics while destabilizing the spheroid ultrastructure. The model serves as a proficient platform for more in-depth elucidation of NP cytotoxicity at the preclinical investigation phase.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 1","pages":"e70051"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896376","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
Intravitreal Administration of Avacincaptad Pegol in a Nonhuman Primate Model of Dry Age-Related Macular Degeneration. 非人类灵长类干性年龄相关性黄斑变性模型玻璃体内注射无活性Pegol。
IF 2.9 4区 医学
Pharmacology Research & Perspectives Pub Date : 2025-02-01 DOI: 10.1002/prp2.70052
Rintaro Fujii, Mayumi Matsushita, Yoshitaka Itani, Aldric Hama, Takahiro Natsume, Hiroyuki Takamatsu
{"title":"Intravitreal Administration of Avacincaptad Pegol in a Nonhuman Primate Model of Dry Age-Related Macular Degeneration.","authors":"Rintaro Fujii, Mayumi Matsushita, Yoshitaka Itani, Aldric Hama, Takahiro Natsume, Hiroyuki Takamatsu","doi":"10.1002/prp2.70052","DOIUrl":"10.1002/prp2.70052","url":null,"abstract":"<p><p>The lack of effective treatments for dry age-related macular degeneration (AMD) is in part due to a lack of a preclinical animal model that recapitulates features of the clinical state including macular retinal pigment epithelium (RPE) degeneration, also known as geographic atrophy (GA). A nonhuman primate model of GA was developed and its responsiveness to an approved treatment, avacincaptad pegol (ACP), a complement C5 inhibitor, was evaluated. Intravitreal (ivt) administration of sodium iodate (SI) into one eye of male Macaca fascicularis leads to retinal areas (mm<sup>2</sup>) of hyper- or hypo-autofluorescence. Qualitative changes to the retinal structure over time were observed with spectral domain optical coherence tomography (OCT). Six days after SI administration, prior to treatment, mean (± SEM) GA of all eyes was 8.2 ± 1.8 mm<sup>2</sup>. Following randomization to treatment groups, either vehicle or ACP was ivt injected and treatment was continued every 4 weeks, for a total of four treatments. Sixteen weeks after SI administration, the GA area in vehicle-treated eyes was 18.9 ± 6.6 mm<sup>2</sup>, whereas GA in ACP-treated eyes was 11.4 ± 4.0 mm<sup>2</sup>, a reduction by about 36%. Increased, followed by decreased, overall macular thickness was observed with OCT over time following SI administration. Treatment with ACP did not change alter macular thickness thinning. Geographic atrophy-like lesions that expand over time are observed following SI administration. The current macaque model could be utilized to further explore the mechanism of dry AMD and to develop more novel therapeutics.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 1","pages":"e70052"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896377","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
Transfer of the Oral Gonadotropin-Releasing Hormone Receptor Antagonist Relugolix Into Breast Milk of Healthy Lactating Women. 口服促性腺激素释放激素受体拮抗剂瑞路高利在健康哺乳期妇女母乳中的转移
IF 2.9 4区 医学
Pharmacology Research & Perspectives Pub Date : 2025-02-01 DOI: 10.1002/prp2.70067
Darin B Brimhall, Yu-Luan Chen, Sarah Lee, Kazumasa Yoshida, Mike Ufer
{"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<sub>max</sub>) of 5.81 h and a geometric mean peak concentration (C<sub>max</sub>) 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}
引用次数: 0
A Clinical Practice-Based Comparison of Conventional and Individualized Dosing Strategies for Therapeutic Enoxaparin. 基于临床实践的依诺肝素治疗的常规和个体化给药策略比较。
IF 2.9 4区 医学
Pharmacology Research & Perspectives Pub Date : 2025-02-01 DOI: 10.1002/prp2.70039
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
{"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}
引用次数: 0
β2-Adrenergic Receptor Agonist Clenbuterol Protects Against Acute Ischemia/Reperfusion-Induced Arrhythmia by Regulation of Akt/eNOS/NO/Cx43 Signaling Pathway. β2-肾上腺素能受体激动剂克仑特罗通过调节Akt/eNOS/NO/Cx43信号通路对急性缺血/再灌注性心律失常的保护作用
IF 2.9 4区 医学
Pharmacology Research & Perspectives Pub Date : 2025-02-01 DOI: 10.1002/prp2.70070
Jing Fu, Li Liu, Qin Fu, Xiaoman Zeng, Xiaoyan Yang
{"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}
引用次数: 0
From Psychiatry to Oncology: Exploring the Anti-Neoplastic Mechanisms of Aripiprazole and Its Potential Use in Cancer Treatment. 从精神病学到肿瘤学:探索阿立哌唑的抗肿瘤机制及其在癌症治疗中的潜在应用。
IF 2.9 4区 医学
Pharmacology Research & Perspectives Pub Date : 2025-02-01 DOI: 10.1002/prp2.70076
Liam A O'Callaghan, Ciara B Blum, Katie Powell, Russ Chess-Williams, Catherine McDermott
{"title":"From Psychiatry to Oncology: Exploring the Anti-Neoplastic Mechanisms of Aripiprazole and Its Potential Use in Cancer Treatment.","authors":"Liam A O'Callaghan, Ciara B Blum, Katie Powell, Russ Chess-Williams, Catherine McDermott","doi":"10.1002/prp2.70076","DOIUrl":"10.1002/prp2.70076","url":null,"abstract":"<p><p>Drug repurposing provides a cost-effective and time-saving approach to cancer therapy. Aripiprazole (ARI), a third-generation antipsychotic, has shown potential anticancer properties by modulating pathways central to tumor progression and resistance. This scoping review systematically examines evidence on ARI's anticancer effects, mechanisms of action, and translational potential. A systematic search of PubMed, EMBASE, SCOPUS, and Web of Science was conducted following PRISMA-ScR guidelines. Eligible studies included in vitro, in vivo, and clinical investigations. Data on cancer types, pathways, assays, and outcomes were extracted and synthesized to identify trends and gaps. Of 588 screened studies, 23 met inclusion criteria, spanning cancer types such as breast, colorectal, lung, and brain cancers. ARI modulates key pathways like PI3K/AKT/mTOR and Wnt/β-catenin, induces apoptosis through mitochondrial dysfunction and ER stress, and overcomes drug resistance by inhibiting P-glycoprotein activity and expression. It exhibits tumor-suppressive effects in vivo and synergizes with chemotherapy and radiotherapy. Retrospective population studies suggest ARI's prolactin-sparing properties may reduce the risk of hormone-sensitive cancers such as breast and endometrial cancer compared to antipsychotics with stronger dopamine receptor blockade. Additionally, ARI's ability to target multiple Hallmarks of Cancer highlights its promise as a repurposed anticancer agent. However, current evidence is primarily preclinical and observational, with limited clinical validation. Large-scale cohort studies and prospective trials are essential to confirm its efficacy and address translational challenges. By bridging these gaps, ARI could emerge as a valuable adjunctive therapy in oncology, leveraging its safety profile and versatility to address unmet needs in cancer treatment.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 1","pages":"e70076"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11821285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410004","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
Non-Linear Dose-Response Relationship for Metformin in Japanese Patients With Type 2 Diabetes: Analysis of Irregular Longitudinal Data by Interpretable Machine Learning Models. 二甲双胍在日本2型糖尿病患者中的非线性剂量-反应关系:通过可解释的机器学习模型分析不规则纵向数据
IF 2.9 4区 医学
Pharmacology Research & Perspectives Pub Date : 2025-02-01 DOI: 10.1002/prp2.70055
Hayato Akimoto, Takuya Nagashima, Kimino Minagawa, Takashi Hayakawa, Yasuo Takahashi, Satoshi Asai
{"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}
引用次数: 0
Part 1: Evaluation of Pediatric Cannabis-Drug Interaction Reports. 第一部分:儿童大麻-药物相互作用报告的评价。
IF 2.9 4区 医学
Pharmacology Research & Perspectives Pub Date : 2025-02-01 DOI: 10.1002/prp2.70046
Maryann R Chapin, Sandra L Kane-Gill, Xiaotong Li, Kojo Abanyie, Sanya B Taneja, Susan Egbert, Mary F Paine, Richard D Boyce
{"title":"Part 1: Evaluation of Pediatric Cannabis-Drug Interaction Reports.","authors":"Maryann R Chapin, Sandra L Kane-Gill, Xiaotong Li, Kojo Abanyie, Sanya B Taneja, Susan Egbert, Mary F Paine, Richard D Boyce","doi":"10.1002/prp2.70046","DOIUrl":"10.1002/prp2.70046","url":null,"abstract":"<p><p>Data addressing safety concerns related to potential drug interactions between cannabis-derived products and pharmaceutical medications in the pediatric population are lacking. In this study, we retrieved case reports through a published literature search using PubMed and spontaneous reporting data using the Food and Drug Administration's Adverse Event Reporting System (FAERS) to identify potential cannabis- and cannabinoid-drug interactions in individuals younger than 18 years old. To evaluate the published case reports, we used the Drug Interaction Probability Scale (DIPS), a 10-item questionnaire designed to discern the causal relationship between a potential drug interaction and adverse drug reactions (ADRs). FAERS reports were deduplicated and analyzed to gather information regarding patient demographics, associated drugs, nature of the ADRs, outcomes, professions of the reporters, and reporting timelines. Seven published case reports and 9142 FAERS ADRs reports were included in the final analysis. Based on the findings, caution is warranted when cannabis or cannabinoids are used in combination with prescribed medications, including methadone, everolimus, fluoxetine, and paroxetine. Cannabinoids may inhibit drug-metabolizing enzymes, including several cytochrome P450s, leading to increased drug exposure and potentially, an increased risk for ADRs.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 1","pages":"e70046"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885289","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
Bridging Traditions and Technology: The Role of Ethnopharmacology in Shaping Next-Generation Multidisciplinary Researchers. 连接传统与技术:民族药理学在塑造下一代多学科研究人员中的作用。
IF 2.9 4区 医学
Pharmacology Research & Perspectives Pub Date : 2025-02-01 DOI: 10.1002/prp2.70074
Ee Wern Tan, Ley Hian Low, Atanas G Atanasov, Bey Hing Goh
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