داروشناسی
مقالهها، منابع و پژوهشهای تازه حوزه داروشناسی
ورود به زیرشاخهنقشه موضوعی
جستوجوی دقیقداروسازی
علوم دارویی، دارودرمانی، ایمنی و فناوری دارو
زیرشاخهها
برای رسیدن به فهرست متمرکزتر، یک مسیر تخصصی را انتخاب کنید.
داروسازی بالینی
مقالهها، منابع و پژوهشهای تازه حوزه داروسازی بالینی
ورود به زیرشاخهفارماسوتیکس و فناوری دارویی
مقالهها، منابع و پژوهشهای تازه حوزه فارماسوتیکس و فناوری دارویی
ورود به زیرشاخهفارماکوگنوزی
مقالهها، منابع و پژوهشهای تازه حوزه فارماکوگنوزی
ورود به زیرشاخهشیمی دارویی
مقالهها، منابع و پژوهشهای تازه حوزه شیمی دارویی
ورود به زیرشاخهسمشناسی
مقالهها، منابع و پژوهشهای تازه حوزه سمشناسی
ورود به زیرشاخهفارماکوویژیلانس
مقالهها، منابع و پژوهشهای تازه حوزه فارماکوویژیلانس
ورود به زیرشاخهاقتصاد دارو
مقالهها، منابع و پژوهشهای تازه حوزه اقتصاد دارو
ورود به زیرشاخهبیوفارماسی و فارماکوکینتیک
مقالهها، منابع و پژوهشهای تازه حوزه بیوفارماسی و فارماکوکینتیک
ورود به زیرشاخهتازهترین رکوردها
شواهد داروسازی
PubMed2026
Chitosan-enhanced mucoadhesive delivery for local action: Salivary pharmacokinetic estimation.
BACKGROUND: Sore throat ache is a discomforting condition for patients during the disease course while eating, drinking or swallowing. However, improved topical concentration of locally acting drugs can address this issue. OBJECTIVES: The goal of the current research was to formulate and evaluate the single-dose salivary pharmacokinetics of a chitosan (CT)-based mucoadhesive delivery system containing tibezonium iodide and lignocaine (LIG). METHODS: Mucoadhesive buccal gels were formulated using a homogenization technique and then subsequently characterized for physical, physicochemical and mucoadhesive properties. The ex vivo mucoadhesive studies were conducted on healthy New Zealand rabbits (aged 12-14 weeks and weight range in between 2.2-2.5 kg). RESULTS: Solid-state characterization revealed the absence of any unusual peaks in the physical mixture of the FTIR and DSC, whereas the unchanged physical form of drugs was confirmed through PXRD analysis. Formulations containing sodium alginate (SA) demonstrated greater swelling (15.39% in F4) but could not sustain drug release for up to 3 h at the polymer concentrations studied. Contrarily, poor mucoadhesive strength (MS) and mucoadhesive flow time (FT) were associated in formulations containing SA. Homogenization of CT and HPMC gels, when mixed at respective concentrations of 1.5% and 2% w/v, demonstrated sustained drug release over time, along with improved MS and FT values of 16.34 g and 142.20 min, respectively. Better salivary concentrations (Cmax) for LIG (5.14 µg/mL) and TIB (4.82 µg/mL) were observed at 2 and 3 h, respectively. CONCLUSION: Our study demonstrated higher Cmax concentrations of the locally acting drugs with single-dose mucoadhesive delivery in healthy volunteers, designed for sore throat, as a single-dose alternative to their respective conventional lozenges.
PubMed2026
Effect of diltiazem sustained-release capsules on cardiorenal composite outcomes in hypertensive patients with coronary heart disease: A real-world propensity score-matched study.
BACKGROUND: Hypertension frequently coexists with coronary heart disease (CHD) and integrated management is essential to reduce cardiovascular and renal complications. OBJECTIVES: To evaluate the efficacy and safety of add-on sustained-release diltiazem capsules in patients with hypertension and CHD. METHODS: This retrospective cohort analysis included 302 consecutive patients with CHD treated at the Affiliated Hospital of Jiangnan University between May 2021 and May 2024. Patients were divided into a control group (n=158) receiving standard guideline-directed therapy and a diltiazem group (n=144) receiving add-on diltiazem sustained-release capsules. Propensity scores were used to match and balance baseline covariates to reduce selection bias. Following matching, intergroup comparisons for baseline characteristics, occurrence of cardiorenal composite endpoints, blood pressure, heart rate (HR) control during follow-up and adverse drug reactions were conducted. Multivariate regression analysis was used to determine predictors of cardiorenal endpoint events. RESULTS: After matching, baseline covariates were well-balanced between groups. During a median follow-up of 18 months, the cumulative incidence of cardiorenal composite endpoint events was lower in the diltiazem group than in controls (16.39% vs. 32.79%, P=0.002). Multivariate Cox analysis showed that diltiazem therapy was independently associated with a lower risk of composite outcomes (hazard ratio = 0.465, 95% CI: 0.284-0.760, P = 0.002). Patients receiving diltiazem also had a lower mean HR and higher achievement rates for HR control and combined blood pressure/HR targets (all P<0.05). The reduction in composite outcomes was primarily driven by fewer heart failure rehospitalizations. Drug-related adverse events were comparable between groups. CONCLUSION: Adding sustained-release diltiazem capsules to standard therapy is associated with a lower cardiorenal composite endpoint risk in patients with hypertension and CHD. The observed benefit was mainly driven by fewer heart failure rehospitalizations, alongwith improved control of blood pressure and heart rate. The renal findings should be considered exploratory because the number of renal events was limited.
PubMed2026
Preparation, characterization and in-vitro anti-cholestatic activity of swertiamarin-loaded galactosylated solid lipid nanoparticle.
BACKGROUND: Cholestatic liver injury (CLI) is a rapidly progressive liver disorder characterized by the accumulation of bile acids (BA). The therapeutic effects of current medicines used to treat CLI are unsatisfactory. OBJECTIVES: This study aimed to prepare galactosylated solid lipid nanoparticle (SLN) with swertiamarin (STM) by using a galactosylated lipid, N-hexadecyl lactobionamide (N-HLBA) and evaluate its anti-cholestasis effect in-vitro. METHODS: The galactosyl-lipid N-HLBA was prepared via the lactone form intermediates of lactobionic acid and synthesized by anchoring galactose to hexadecylamine lipid. The STM-loaded galactosylated SLN (STM-GalSLN) was successfully prepared by a melt-emulsification-ultrasound method. The prescription was optimized by orthogonal test. The morphology was observed by transmission electron microscope. The particle size and zeta potential were determined by laser granularity equipment. The encapsulation efficiency (EE) and drug loading capacity (DL) were determined by ultrafiltration, centrifugation and HPLC method. RESULTS: The optimized prescription was as follows: 50 mg of STM, 20 mg of N-HLBA, 500 mg of glyceryl behenate, 400 mg of soybean lecithin, 200 mg of poloxamer188 and 500 mg of Tween 80. The STM-GalSLN was spherical in shape and its particle size, zeta potential, EE and DL were 164.40 ±4.68 nm, -14.53 ±3.20 mV, 82.41 ±2.88 % and 0.32 ±0.02 %, respectively, and the EE of STM-GalSLN did not change significantly over 30 days at 4°C. Furthermore, STM-GalSLN alleviated cholestatic liver injury (CLI) in a concentration-dependent manner in-vitro. CONCLUSION: The findings from this study indicated that the melt-emulsification-ultrasound method was rational and reliable, which provided an experimental basis for developing a new nano preparation of STM for CLI.
PubMed2026
Flibanserin safety in real-world use: a decade of US Food and Drug Administration Adverse Event Reporting System pharmacovigilance evidence.
BACKGROUND: Flibanserin, a centrally acting 5-HT1A agonist and 5-HT2A antagonist, is the first approved therapy for acquired, generalized hypoactive sexual desire disorder in premenopausal women. Despite its clinical availability, post-marketing data on real-world safety remain limited. METHODS: A retrospective pharmacovigilance analysis was conducted using the US Food and Drug Administration Adverse Event Reporting System from 2016 to 2025. Duplicate removal, data harmonization and standardized MedDRA coding were applied. Only reports in which flibanserin was designated as the primary suspect drug were included. Disproportionality analyses using proportional reporting ratio, reporting odds ratio, information component and empirical Bayes geometric mean algorithms identified flibanserin-associated safety signals. Sensitivity analyses were conducted according to recorded concomitant medication status. RESULTS: A total of 1702 adverse event reports were identified, with 95% involving women. Most events were non-serious and occurred within the first week of therapy (median onset: 3 days). Prominent signals were nervous system and psychiatric disorders, notably somnolence, dizziness, insomnia and fatigue. Additional signals included hypotension, orthostatic hypotension and product use in unapproved populations, suggesting off-label exposure. Central nervous system-related signals remained directionally consistent in flibanserin-only and concomitant-medication cohorts, whereas hypotension was prominent among reports with recorded concomitant medications. CONCLUSIONS: Flibanserin's real-world safety profile is largely consistent with preapproval data, dominated by early-onset, reversible central nervous system reactions linked to its serotonergic mechanism. However, persistent hypotension and off-label or product-use-related reports underscore the need for continued pharmacovigilance, clinician education, and strict adherence to Risk Evaluation and Mitigation Strategy requirements to maintain an optimal benefit-risk balance.
PubMed2026
A Retrospective Evaluation of a Pharmacist-Driven Urgent Care Microbiology Review Program.
BACKGROUND: Pharmacist-driven microbiology review programs have been thoroughly described in the emergency department setting. However, there is limited evidence for programs in outpatient settings, especially for urgent care settings. The purpose of this study is to evaluate a pharmacist-driven urgent care microbiology review program to determine the impact of its implementation. METHODS: This retrospective cohort study evaluated urgent care patients who did not receive appropriate treatment based on urine, wound, or respiratory culture, or select sexually transmitted infection testing. A pharmacist-driven microbiology review program at two urgent cares was compared to 11 other urgent cares using only physician/advanced practice provider (APP) review of microbiology results. The primary end point was the time to appropriate treatment in hours from finalized result to prescription of appropriate treatment. Secondary end points included time to appropriate treatment in calendar days and unplanned 30-day revisit rate. RESULTS: A total of 400 patients were included in this study (pharmacist-driven, n = 200; physician/APP, n = 200). Time to appropriate treatment in hours was 11 h in the pharmacist-driven cohort and 13 h in the physician/APP cohort (p = 0.047). Unplanned 30-day revisit rate was similar between the two groups (pharmacist-driven 14% versus physician/APP 12.5%, p = 0.658). CONCLUSION: A pharmacist-driven urgent care microbiology review program achieved a similar time to appropriate antimicrobial treatment compared with a physician/APP process while maintaining comparable clinical outcomes.
PubMed2026
Contribution of Countries and International Collaboration in Clinical Pharmacology Research. A Cross-Sectional Bibliometric Study of Six Top Ranked Specialty Society Journals.
There are no bibliometrics analyses on articles published in clinical pharmacology journals. We aimed to determine the countries in which authors of original investigations or meta-analyses were based and their international collaboration. This is a cross-sectional study conducted in six journals linked to learned clinical pharmacology societies/associations. For each journal, we started with the June-2025 issue and searched backward for articles meeting the selection criteria until 100 were identified or the January-2024 issue was reached. To calculate the credit by country, we used the complete fractionalized counting (CFC) method for assessing authors' contribution considering only the country of the authors included in the byline. CFC awards 1 credit among all authors and countries. A total of 503 articles were included in the analysis: 100 from four journals and 79 and 24 from the other two. Investigators from 66 countries from all continents contributed as authors; 46 countries provided lead authors. All but one were multi-authored articles; 9% were authored by international teams (range among the six journals: 16%-41%). Of the 503 credits, top countries were the United States (99.14), China (76.14), Japan (31.65), Denmark (28.69) and the Netherlands (27.29). The 17 EU countries obtained 151.86 credits (30.2% of the total). Among the top 25 countries, only five were not high-income countries. This exploratory analysis showed that with limited international collaboration, the authors of these studies worked mainly in wealthy countries, except for China.
PubMed2026
Design-Expert Assisted Formulation Development, Optimization, and Evaluation of Selegiline and Biochanin A Loaded Self-Nanoemulsifying Drug Delivery System.
The goal of the work was to formulate, optimize, and evaluate liquid-Self-nanoemulsifying drug delivery system (L-SNEDDS) co-loaded with Selegiline (SEL), a monoamine oxidase type B (MAO-B) inhibitor, and Biochanin A (BCA), a potent adjunctive neuroprotective agent found in Trifolium pratense, to enhance oral delivery and accelerate anti-Parkinsonian efficacy for the management of Parkinson's disease (PD). Propylene glycol was chosen as co-surfactant, Tween 80 as surfactant, and peppermint oil as oil phase after excipients screening, as this combination exhibited the broadest emulsification region in pseudo-ternary phase diagram. A systematic Quality-by-Design (QbD) approach was adopted, and formulation variables were optimized using Design-Expert software to obtain an optimized L-SNEDDS formulation with desirable physicochemical attributes. Dilution of the optimized SNEDDS led to the spontaneous formation of a stable aqueous nanoemulsion exhibiting a droplet size of 110.9 nm, polydispersity index (PDI) 0.265, transmittance of 98.86 ± 0.37%, zeta potential of -16.3 mV, viscosity of 6.35 ± 2.51 cP, self-emulsification time of 27.35 s, and conductivity of 196.23 ± 0.324 μS cm-1. In vivo studies showed that SEL-BCA-loaded SNEDDS exhibited better oral bioavailability than pure SEL-BCA suspension. Notably, SNEDDS achieved higher brain Cmax values for SEL (5.6 ± 0.41 μg mL-1) and BCA (13.84 ± 1.14 μg mL-1), as well as elevated plasma concentrations of SEL (6.51 ± 0.43 μg mL-1) and BCA (762.65 ± 16.82 μg mL-1). Collectively, the results underscore the potential of the SEL-BCA SNEDDS as a combinational delivery platform that could improve the effectiveness of combination therapy for the management of PD.
PubMed2026
European Society of Clinical Pharmacy: bridging gaps-clinical pharmacy in the digital transition of care.
چکیده ثبت نشده است.
PubMed2026
Key Performance Indicators for Clinical Pharmacy Practice and Administration in Inpatient/Acute Care Settings: An Opinion of the Clinical Administration Practice and Research Network of the American College of Clinical Pharmacy.
Key performance indicators (KPIs) are quantifiable measures that describe critical success factors of an organization. Their vital role in ensuring the delivery of quality health care services necessitates the development of KPIs relevant to inpatient clinical pharmacy practice. This opinion paper from the American College of Clinical Pharmacy (ACCP) Clinical Administration Practice and Research Network (CADM PRN) describes the rationale, methodology, and outcomes of a consensus process to identify a focused set of inpatient/acute care clinical pharmacy KPIs. Leveraging a modified Delphi approach, the CADM PRN convened an Expert Panel of clinical pharmacy leader members to build a consensus-driven set of KPIs reflecting clinical, operational, patient-centered, and financial contributions of clinical pharmacists in the inpatient/acute care setting. From a previous ACCP White Paper, a total of 15 KPIs were identified across four domains: (1) clinical practice and patient safety, (2) clinical outcomes and readmissions, (3) medication education and patient engagement, and (4) financial and operational value. The CADM PRN posits that the establishment and implementation of standardized KPIs are essential for measuring and demonstrating the value of clinical pharmacy services in modern health care, offers pragmatic, consensus-based KPIs for evaluating clinical pharmacy services supporting resource justification, and advancing the visibility and impact of pharmacists in acute care practice. As hospitals shift toward value-based care, robust KPI frameworks will be critical for optimizing patient outcomes, supporting financial sustainability, and justifying appropriate staffing. Future efforts should focus on pilot testing, addressing implementation barriers, and achieving broader acceptance for KPIs across the profession.
PubMed2026
Mapping Current Use of Artificial Intelligence in Pharmacology Education via a Scoping Review.
Pharmacology education, often reputed as complex, overtly didactic and decontextualised, may benefit from artificial intelligence-supported strategies. However, current guidance is fragmented across disciplines and contexts, thus weakening evidence-based curricular implementation. This scoping review mapped existing research to identify applications, strengths, limitations, and areas for future development. A double-blinded screening process facilitated by Covidence yielded 17 eligible studies from four databases. Studies mostly comprised cross-sectional studies from high-income countries in the medical context, with generative artificial intelligence being predominant (ChatGPT-3.5 and ChatGPT-4.0). Research comprised assessment (n = 12), paedagogy (n = 4), curriculum design (n = 1), and programme evaluation (n = 1). Most studies assessed tools' ability to answer examinations, with mixed success depending on the version, question type, and inclusion of context in prompt engineering. Few studies incorporated students, limiting insights into learning impact. Zero-shot prompting was mostly used, limited further by unclear design frameworks, which may bias outcomes considering downstream inefficiencies. Current research prioritises the performance of artificial intelligence, rather than its integration or impact in learning, which reduces its applicability for curriculum design and competency development. Although promising, the impact is limited, requiring clearer instructional design and rationalisation within the education ecosystem. Although there is considerable potential for pharmacology education, research requires greater structure, longitudinal design, and incorporation of students to inform clear impact. Purposeful, context-aligned implementation and continuous evaluation are needed to ensure ethical, valid, and meaningful use in pharmacology education. To support future research, recommendations are provided for practical reporting, scientific design, and impact measurement.
PubMed2026
Music-Based Interventions in Clinical Pharmacy Practice: A Narrative Review of Mechanisms, Evidence, and a Framework for Integration.
Music-based interventions (MBIs) have emerged as a promising, nonpharmacologic approach to improving patient care across a variety of clinical settings. This narrative review examines the current evidence describing the mechanistic basis through which music engages biological pathways relevant to clinical pharmacy practice, and the clinical evidence supporting MBIs as adjuncts to pharmacotherapy across clinical outcomes. From this evidence, the review proposes a framework through which MBIs may be integrated into clinical practice that comprises: (1) patient selection, (2) MBI selection, and (3) outcome monitoring. The review does not constitute formal practice guidance, as pharmacy-specific clinical protocols and implementation models remain active areas of research. Additionally, the review synthesizes emerging evidence supporting MBIs as a clinical pharmacy workforce well-being strategy. Collectively, these findings highlight the potential for MBIs to serve as an innovative adjunct to traditional pharmacotherapy that aligns with the clinical pharmacist's existing responsibilities for medication optimization, deprescribing, and holistic, patient-centered care.
PubMed2026
Promoting Sustainable Prescribing-A Case Study Presenting Experiences From Two Swedish Drug and Therapeutics Committees.
During the past two decades, it has become evident that pharmaceuticals is an emerging environmental problem. In this study, we present the experiences from two Swedish Drug & Therapeutics Committees (DTCs) on how they integrate environmental considerations into their formularies and continuous professional education activities. A cross sectional study was performed describing activities to promote sustainable prescribing conducted during two decades by the DTCs in the Swedish regions of Gävleborg and Västernorrland, along with trends in sales of diclofenac and fluoroquinolones between 2000 and 2024. The two DTCs integrate environmental considerations in their formularies and continuous professional education activities. Further acitivities include monitoring of prescribing, dialogue with water suppliers and pharmacies, as well as information and communication to the general public. The total utilization of diclofenac for systemic use peaked with 127 kg in Gävleborg and 137 kg in Västernorrland in 2011, after which the amounts declined. The topical formulations were mainly sold as over-the-counter and increased until 2016, when it started to decline. The amounts of ciprofloxacin and norfloxacin increased until 2012 when they started to decline. This case study from two Swedish regions illustrates how environmental considerations can be incorporated into the DTC's mission to promote rational and responsible medication use. We believe it may be valuable for different stakeholders to show potential ways in how to promote a more sustainable use of medicines.
PubMed2026
Risk of Major Malformations Following First-Trimester Exposure to Cariprazine: Preliminary Data From the MGH National Pregnancy Registry for Psychiatric Medications.
OBJECTIVE: Systematically collected pregnancy safety data for cariprazine have been lacking, despite growing use of this medication across psychiatric indications. The goal of this analysis was to determine the risk of major malformations among infants of mothers with psychiatric illness who used cariprazine during the first trimester of pregnancy compared to unexposed controls. METHODS: The National Pregnancy Registry for Psychiatric Medications (NPRPM) is a prospective pharmacovigilance program in which pregnant women with psychiatric diagnoses are enrolled during pregnancy and followed through the postpartum period. Labor and delivery and pediatric medical records are reviewed for evidence of major malformations followed by final adjudication by a dysmorphologist blinded to medication exposure. Infants with first-trimester exposure to cariprazine were compared to controls not exposed to second-generation antipsychotic medications. RESULTS: As of September 9, 2025, N = 4,125 have enrolled in the study. Of those enrolled, 58 cariprazine-exposed infants and 2,098 infants in the comparison group were eligible for inclusion in this analysis. There were no major malformations in the cariprazine-exposed group (absolute risk 0.00%; 95% confidence interval, 0.00%-6.16%) compared to 32 infants with major malformations in the control group (1.53%; 1.05%-2.15%). CONCLUSIONS: In this prospective cohort, 0 of 58 infants exposed to cariprazine during the first trimester had major malformations, compared with 32 of 2,098 (1.53%) unexposed infants. Although these data are preliminary and cannot rule out modest teratogenic effects, they are nonetheless important to provide to health care providers and the public, as cariprazine use has been rising among women of reproductive age.
PubMed2026
Student Perceptions of a Virtual Reality Animation for Teaching Absorption and Bioavailability in Pharmacology: A Mixed Methods Evaluation.
Medication errors, often arising from insufficient pharmacology knowledge, can have serious consequences, highlighting the importance of effective pharmacology education for health care students. This study hypothesized that virtual reality (VR) could improve student engagement, motivation and perceived learning of core concepts in pharmacology. A mixed-method approach was employed. Students who had completed a course in basic pharmacology were recruited from five international study sites to view a VR animation, explaining drug absorption and bioavailability. The students responded to an online questionnaire exploring their experience and understanding. In addition, 13 medical students from the University of Bergen participated in focus group interviews to further explore their perceptions of VR in pharmacology education. A total of 133 students participated in the VR session and completed the questionnaire, with approximately half reporting that the VR animation changed their understanding of drug absorption. Thematic analysis of the focus group interviews produced three themes descriptive of the students' learning experiences, each pivoting tensions between: (1) The role of VR in integrating pharmacology with other medical disciplines; (2) striking a balance between engaging and overwhelming learning experiences; (3) in-depth learning under the weight of assessment. The technical solution appears satisfactory, and students found the 360° VR animation engaging and useful for visualizing the complex concepts of absorption and bioavailability. VR animation shows potential to enhance integration of pharmacology to other medical disciplines. However, careful design is required to support self-paced learning and minimize cognitive overload.
PubMed2026
Using Pharmacovigilance Data for Signal Detection of Drug Interactions for Rosuvastatin.
The 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor rosuvastatin is a substrate of breast cancer resistance protein (BCRP). BCRP inhibition increases rosuvastatin plasma concentrations and may result in concentration-dependent muscle toxicity, at worst rhabdomyolysis. We investigated if concomitant use of rosuvastatin and drugs identified as in vitro BCRP inhibitors shows an increased number of rhabdomyolysis events based on pharmacovigilance data. From reports in the US Food and Drug Administration Adverse Event Reporting System for patients using rosuvastatin, we formed interaction (rosuvastatin with inhibitor) and non-interaction (rosuvastatin without inhibitor) groups for 71 BCRP inhibitors. These groups were further divided into subgroups with or without rhabdomyolysis. For each inhibitor, we calculated reporting odds ratio (ROR) and 95% confidence intervals (CIs). We identified 9777 individual rosuvastatin-related reports during 2013-2023, including 815 rhabdomyolysis reports. Of the 71 inhibitors, 19 had enough reports for analysis. Significantly increased RORs were obtained for the clinical BCRP inhibitors febuxostat (ROR 2.47, 95% CI 1.38-4.43) and ticagrelor (ROR 4.15, 95% CI 3.32-5.20). Amiodarone, erlotinib and rifampicin showed significantly increased RORs. Our findings support known interactions involving febuxostat and ticagrelor and suggest that also other BCRP inhibitors may increase the risk of rosuvastatin-induced rhabdomyolysis.
PubMed2026
Quantitative indices reveal the importance of medicinal plants in traditional healthcare from rural arid region.
In the present study, quantitative ethnobotanical knowledge of medicinal plants utilized by the local communities for treating different human ailments in selected rural villages of Punjab, Pakistan has been documented. Semi-structured interviews and field surveys were employed to conduct field investigations from March 2024 to April 2025, with a total of 105 informants aged 18-70 years. The total number of plant species recorded and reported for the cure of 14 human ailments was 50 belonging to 25 families. Fabaceae was the dominant family with 6 species, among the documented families. The most abundant life form was herbs (26 species) and the most common part used was leaves (16 species). The highest Relative Frequency of Citation (RFC = 0.34) was found in Bombax ceiba, Cenchrus echinatus and Sonchus oleraceus. Spinacia oleracea had the highest Use Value (UV = 0.08) while the lowest UV was 0.03. Mentha canadensis recorded the highest Fidelity Level (FL = 93%) for the treatment of hyperacidity and diarrhea whereas Azadirachta indica recorded the lowest FL (69%) in the treatment of scabies and pimples. Three species recorded the highest FC (36) while three other species recorded the lowest FC (24). The results showed a high diversity of medicinal plants in the study area and significant traditional ethnobotanical knowledge. There were not enough up-to-date health care facilities in rural areas, so local residents heavily depended on the use of medicinal plants for basic health care. The study emphasized the need to maintain the knowledge of the indigenous people and conserve medicinal plants resources for sustainable use and future exploration in medicine.
PubMed2026
AI-guided data-driven kinetic modelling carbon quantum dot-enabled pH-responsive CMC/CeO2 nanocarriers for quercetin delivery and in vitro evaluation in lung cancer cells.
This work reports the development and systematic evaluation of a carboxymethyl cellulose (CMC)-based nanocarrier system co-loaded with cerium oxide (CeO2) and carbon quantum dots (CQDs) for pH-responsive delivery of quercetin (QC) and in vitro evaluation in lung cancer cells. The nanocarriers were prepared using a water-in-oil-in-water (W/O/W) double emulsion approach, yielding spherical particles with an average size of approximately 134 nm and a high positive surface charge (+66 mV), indicative of favourable colloidal stability. FESEM analysis confirmed a uniform morphology and compact internal structure. The incorporation of CeO2 appears to reinforce the polymer matrix, contributing to improved drug encapsulation. The optimized formulation exhibited high encapsulation efficiency (88%) and drug loading capacity (47%), outperforming CeO2-free systems. In vitro release studies demonstrated a clear pH-dependent biphasic behaviour, with significantly faster release under pH 5.4 compared to physiological pH (7.4), reaching 98% and 58% after 96 h, respectively. Drug release followed the Higuchi model, suggesting diffusion-controlled kinetics, while the Korsmeyer-Peppas model indicated a non-Fickian mechanism. An AI-guided nonlinear modelling workflow was used to extract interpretable kinetic descriptors directly from experimental release data. Biological evaluation revealed enhanced anticancer activity against A549 cells, with viability reduced to 49.1%, while maintaining high biocompatibility towards L929 cells.
PubMed2026
Assessing the risk of cataracts associated with medications: A pharmacovigilance analysis of the FAERS database.
Cataracts are a leading cause of global blindness and visual impairment, with drug-induced cataracts emerging as a significant yet understudied contributor. This study aimed to comprehensively and systematically investigate medication-related cataract risk signals using data from the FDA Adverse Event Reporting System. We searched the FDA Adverse Event Reporting System database for all reported cases of medication-related cataracts from October 2014 to September 2024. Disproportionality analysis, employing the information component and reporting odds ratio, identified the medications most commonly associated with cataracts. Demographic characteristics, drug categories, and time-to-onset were also evaluated. After deduplication, 37,838 cataract-related reports were included. A total of 588 drugs were linked to cataracts. The top 50 medications with the highest signal association strength were identified based on information component values, including anti-cancer agents, immunomodulators, glucocorticoids, adrenergic medications, and anticholinergic medications. Mirvetuximab soravtansine, nitisinone, and belantamab mafodotin demonstrated the strongest signals. Most cases involved individuals over 60 years old, with females accounting for 68.7% of the reports. Significant variability in time-to-onset was also observed. In conclusion, this large-scale signal detection analysis utilizes real-world data to provide a comprehensive list of medications potentially associated with cataracts. Future research is required to validate these statistical associations.
PubMed2026
Disproportionality analysis of sex-stratified adverse event signals in growth impairment: Insights from the FDA adverse event reporting system.
This study aimed to examine sex-disaggregated adverse event signals associated with growth impairment in pediatric patients, utilizing data from the FDA adverse event reporting system, with a particular focus on growth hormone and related therapeutic agents. A disproportionality analysis was performed on FDA adverse event reporting system data spanning 2004 Q1 to 2025 Q1. The analysis encompassed 3281 growth impairment-related reports, disaggregated by gender, employing Reporting Odds Ratios (ROR) and proportional reporting ratios for signal detection, with temporal patterns assessed via Weibull distribution modeling. Significant sex-disaggregated disparities in safety signals were identified. Somatropin exhibited a stronger association with growth impairment in females (ROR 76.85, 95% CI 65.52-90.15) than in males (ROR 37.31, 95% CI 32.99-42.20). Deflazacort showed a male-exclusive signal (ROR 58.25, 95% CI 41.27-82.21), while imatinib displayed a higher risk in females (ROR 15.55, 95% CI 11.29-21.42) compared to males (ROR 4.17, 95% CI 2.91-5.99). Temporal analysis revealed an early-failure pattern, with 50.6% of events occurring within 180 days. These findings generate the hypothesis that sex-disaggregated pharmacovigilance in pediatrics, particularly for growth-modulating therapies, may reveal differential reporting patterns. Should these signals be validated in controlled prospective studies, they could inform the development of customized monitoring frameworks and dosing strategies aimed at potentially mitigating risks in hypothesized high-risk subgroups.
PubMed2026
Post-marketing safety analysis of nafamostat: A retrospective pharmacovigilance study using the Japanese Adverse Drug Event Report (JADER) database.
Nafamostat is a broad-spectrum serine protease inhibitor approved for pancreatitis, disseminated intravascular coagulation, and extracorporeal circulation anticoagulation. It also showed potential anti-SARS-CoV-2 activity during the COVID-19 pandemic, leading to expanded clinical use. This study aimed to explore post-marketing adverse event (AE) signals of nafamostat based on the Japanese Adverse Drug Event Report database so as to provide evidence for clinical safety management. Retrospective analysis was performed on AE reports retrieved from the Japanese Adverse Drug Event Report database between Q1 2004 and Q3 2024. Four disproportionality analysis algorithms, including reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker, were adopted to detect AE signals. The distribution of AEs across system organ classes and preferred terms was summarized, and the time to onset was analyzed using the Weibull shape parameter test. A total of 2051 valid AE reports with nafamostat as the primary suspected drug were included, covering 20 system organ classes. The most prominent signals were observed in immune system disorders (n = 997) and vascular disorders (n = 370). Twenty-four preferred terms met the screening criteria of all 4 algorithms, among which anaphylactic shock (n = 746), shock (n = 341), and hyperkalemia (n = 200) were the most frequently reported. Six potential novel signals not recorded in the drug label were identified, namely acquired factor V deficiency, increased viral load, burning sensation, retroperitoneal hemorrhage, abdominal wall hematoma, and device-related thrombosis. Further bias analysis confirmed that 3 signals were false-positive results caused by confounding by indication or protopathic bias, while burning sensation had clear biological plausibility. The median time to onset was 1 day (interquartile range: 1-9 days); 58.55% of AEs occurred on the 1st day of administration, and 82.63% developed within 30 days. The Weibull test indicated that the AE risk peaked at the initial medication stage and gradually decreased over time. This real-world study clarified the safety profile of nafamostat, identifying severe allergic reactions and hyperkalemia as the main AEs. Of 6 initially detected unlabeled signals, 3 were confirmed as false-positive due to confounding bias, while the remaining 3 (bleeding complications and abnormal burning sensation) warrant clinical monitoring. Close monitoring within 24 hours after administration is highly recommended to reduce drug-related risks.
PubMed2026
Real-world adverse event profiles of Zuranolone and Brexanolone based on FAERS and VigiAccess databases: An observational study.
Zuranolone and Brexanolone are Food and Drug Administration-approved novel agents for postpartum depression, yet real-world post-marketing safety data for the two drugs remain insufficient. This study aimed to systematically characterize their adverse event (AE) profiles via two authoritative pharmacovigilance databases, namely the Food and Drug Administration Adverse Event Reporting System (FAERS) and VigiAccess. FAERS data from Q1 2019 to Q3 2025 and VigiAccess data updated to November 2025 were extracted. Reporting odds ratio and proportional reporting ratio were adopted to screen and compare AE signals of the two drugs. A total of 631 primary suspect (PS) drug reports for Zuranolone and 102 for Brexanolone were extracted from FAERS, whereas 863 Zuranolone and 227 Brexanolone reports were obtained from VigiAccess. At the system organ class level, AEs associated with Zuranolone involved 22 SOCs in FAERS and 24 SOCs in VigiAccess, with the top three SOCs sorted by reported cases as follows: Nervous system disorders, Psychiatric disorders, and General disorders and administration site conditions (FAERS); Nervous system disorders, General disorders and administration site conditions, and Psychiatric disorders (VigiAccess). For Brexanolone, AEs retrieved from FAERS involved 16 SOCs, compared with 21 SOCs in VigiAccess; the top three SOCs by the number of reported cases were Injury, poisoning and procedural complications, General disorders and administration site conditions, and Psychiatric disorders. After signal screening in the FAERS database, a total of 78 positive signals (involving 9 SOCs) were identified for Zuranolone, whereas 10 positive signals (involving 4 SOCs) were detected for Brexanolone. Four SOCs were commonly implicated in the positive AE signals of both drugs, with the most commonly reported AEs including gait disturbance, exposure via breast milk, fatigue, and therapy cessation. Additionally, compared to Brexanolone, 5 SOCs were uniquely associated with Zuranolone, with the most commonly reported AEs such as vertigo, vision blurred, muscle twitching, somnolence, and loss of personal independence in daily activities. Zuranolone's AEs mainly involved nervous system disorders and Psychiatric disorders, while Brexanolone's primarily included Injury, poisoning and procedural complications, and Psychiatric disorders. This study would provide more safety reference data for the clinical use of two drugs.
PubMed2026
AI for Causality Assessment in Pharmacovigilance: Protocol for a Scoping Review.
BACKGROUND: Pharmacovigilance aims to protect patient safety by identifying and managing adverse events associated with pharmaceuticals. Determining the causality of these adverse events is central at both the individual case and population levels; however, it is increasingly challenging as the volume and complexity of safety data grow. Although AI and related technologies have been proposed to support causality assessment, limited research has examined how these methods are used, their information and quality requirements, or how associated risks are addressed. OBJECTIVE: This scoping review aims to determine the available evidence on AI-based methods for causality assessment in pharmacovigilance. The primary objective is to characterize how these methods are applied or proposed with a focus on their functional roles, reported data inputs and information needs, and associated risks. Secondary objectives include comparing applications at the individual case and population levels; describing the types of AI-based techniques and automation tools used in causality assessment workflows; and summarizing reported data quality considerations and governance mechanisms, including risk management approaches. METHODS: Sources describing or proposing AI-based approaches, including data-driven models (machine learning, natural language processing, knowledge graphs, and causal inference) and knowledge- or rule-based systems implementing causal assessment logic, will be eligible. Searches will be conducted in PubMed, Web of Science Core Collection, ProQuest, EBSCOhost, and Ichushi Web and will be restricted to English- and Japanese-language sources. Two reviewers will independently screen records and full-text articles, with disagreements resolved by a third reviewer. Data will be charted on use cases, information inputs, data quality dimensions, model characteristics, governance mechanisms, and identified risks. Synthesis will follow a reflexive thematic analysis approach and be reported in accordance with PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) guidelines informed by applicable PRISMA-S (Preferred Reporting Items for Systematic reviews and Meta-Analyses literature search extension) elements. RESULTS: This protocol was registered in the Open Science Framework platform on December 23, 2025. The registration was subsequently updated on May 19, 2026, to reflect an extension to the data collection period. A preliminary database search was conducted in December 2025, retrieving a total of 760 records, of which the preliminary title and abstract screening identified 196 (25.8%) articles for full-text review. Database searches are scheduled for July 2026. Data charting is scheduled for August 2026, and synthesis is scheduled for September 2026. Findings are expected to be submitted for publication by the end of December 2026. CONCLUSIONS: This review is expected to provide a structured map of AI-based applications for causality assessment in pharmacovigilance, clarify reported information inputs and data quality dimensions, and synthesize risk management and governance approaches. The findings are expected to inform methodological development, practical implementation, and the governance of AI-supported causality assessment. TRIAL REGISTRATION: Open Science Framework 10.17605/OSF.IO/QVF5C; https://osf.io/qvf5c/overview. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/101691.
PubMed2026
Selected highlights from the 26th International Workshop on Clinical Pharmacology of HIV, Hepatitis, and Other Antiviral Drugs.
Clinical pharmacology plays a crucial role in the successful treatment and prevention of HIV and other viral infections. Information from the field of clinical pharmacology leads to the development of novel antiviral treatments, supports the evaluation of efficacy and safety of antiviral therapies, informs the management of drug-drug interactions, and defines the optimal dosing and drug selection for special populations. The International Workshop on Clinical Pharmacology of HIV, Hepatitis, and Other Antiviral Drugs recently held its 26th meeting. This review focuses on selected abstracts presented at the 2025 workshop and provides insights to assist clinicians in applying this new knowledge to clinical practice.
PubMed2026
Signal mining and analysis of adverse events associated with Isotretinoin: A 20-Year real-world pharmacovigilance study based on FAERS and EudraVigilance databases.
OBJECTIVE: To systematically characterize the post-marketing safety signals of isotretinoin using real-world data from the U.S. FDA Adverse Event Reporting System (FAERS), with independent external validation in the European EudraVigilance (EV) database. METHODS: Adverse event (AE) reports in FAERS from 2004Q1 to 2024Q3 were analyzed. Signal detection was conducted using four complementary disproportionality algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS). Signals concurrently detected by all four methods were defined as robust. Key findings were subsequently examined in EV as an external reference. RESULTS: Among 50,519 patients contributing 142,160 isotretinoin-associated AE reports, 469 statistically robust signals were identified, spanning 25 system organ classes (SOCs). Signals were most concentrated in psychiatric disorders (75, 15.99%), gastrointestinal disorders (58, 12.37%), and congenital, familial, and genetic disorders (50, 10.66%). The strongest association was observed for inflammatory bowel disease (IBD; ROR = 579.14); however, temporal clustering and reporter-type profiling suggested substantial stimulated reporting, potentially driven by litigation, warranting cautious interpretation. Several high-ranking signals were not described in current product labeling, including nasal vestibulitis, hypertrophic anal papilla, and SAPHO syndrome. Pregnancy-related signals were prominent, with unintended pregnancy showing a strong signal (ROR = 91.39). External validation in EV demonstrated high concordance, supporting the robustness and reproducibility of the findings. CONCLUSIONS: Isotretinoin is associated with a broad spectrum of pharmacovigilance signals, with disproportionate representation of psychiatric, gastrointestinal, and pregnancy-related events. While multiple previously unlabelled signals emerged, their clinical relevance remains to be established. These findings underscore the need for strengthened clinical monitoring, rigorous pregnancy prevention strategies, and careful interpretation of spontaneous reporting data.
PubMed2026
Spatial metabolomics in medicinal plant research: current advances, technical challenges, and future perspectives.
Secondary metabolites derived from medicinal plants represent a critical resource for drug discovery and play an indispensable role in the prevention and treatment of major human diseases. Spatial metabolomics has emerged as a transformative approach that overcomes the inherent limitations of traditional metabolomics, particularly tissue homogenisation, by enabling precise, in situ profiling of the spatial heterogeneity and dynamic accumulation of key bioactive compounds. When integrated with complementary technologies such as spatial multi-omics (SMO), single-cell analysis, and artificial intelligence (AI)-assisted imaging, this paradigm provides a powerful framework for deciphering the spatiotemporal regulatory networks that govern secondary metabolite biosynthesis. This review systematically compares conventional and spatial metabolomics, synthesises recent advances in medicinal plant research, critically evaluates current technical challenges and optimisation strategies, and outlines future directions enabled by multi-omics integration and intelligent computational analytics. Collectively, these insights aim to establish a theoretical foundation for the in-depth investigation of medicinal plants and to support their translational application and industrial advancement.
PubMed2026
Herbal and functional food phytochemicals in chronic disease: modulating oxidative stress and health outcomes.
Oxidative stress, described as an imbalance between the production of reactive oxygen species and antioxidant systems, has an important pathogenic role in many chronic diseases, such as cancer, cardiovascular disease, diabetes mellitus, stroke, and neurodegeneration. This narrative review investigates the effect of common herbal medicines and functional foods in oxidative stress, based on available experimental and clinical data. Curcuma longa, Emblica officinalis, Zingiber officinale, berries, and leafy vegetables, which contain bioactive molecules like polyphenols, flavonoids, and terpenoids, have been shown to have antioxidant and anti-inflammatory properties through activation of Nrf2 and NF-κB signalling pathways. The important findings from this review suggest that curcumin and gingerol possess anticancer properties via the regulation of p53, MAPK, and ROS-JNK pathways, which induce apoptosis in cancer cells. Moreover, these bioactive compounds improve mitochondrial dysfunction and redox status in cardiovascular diseases. Bacosides and withanolides can be used for neuroprotection by preventing oxidative injury and protein aggregation in neurodegenerative diseases. The antioxidant-rich herbs and functional foods may have promising roles in oxidative stress-related disorders as preventative and supportive treatment options; however, further research is needed to establish their efficacy and safety in patients.
PubMed2026
Phytotherapeutics self-microemulsifying systems in pellet dosage form for enhanced intestinal drug delivery: formulation, stability, and in-vivo performance.
Self-microemulsifying drug delivery systems (SMEDDS) containing volatile phytotherapeutics such as thymol (T), carvacrol (C), and eugenol (E) present significant formulation challenges, even when solidified. Their instability and interactions with coatings often hinder intestinal delivery. To address these limitations, we developed solid SMEDDS consisting of pellets (microcrystalline cellulose/magnesium aluminometasilicate/chitosan) and enteric capsules (CEC) for enhanced intestinal delivery. Based on solubility and pseudo-ternary phase diagrams, SMEDDS formulations (SES1-3) differing in component ratios (glycerol monooleate/caprylocaproyl macrogol-8 glycerides/diethylene glycol monoethyl ether) with 5% w/w of each drug were identified, demonstrating nano-scale droplet sizes (PDI <0.4) and showing no phase separation over 6 months. Thermodynamic stability and liquid-state NMR revealed particle size variations with preserved structural integrity. The lead formulation SES1 exhibited superior ex-vivo intestinal permeation (T-SES1). CECs filled with T-, C-, and E-loaded SES1 pellets, respectively, prepared via extrusion/spheronization, exhibited in-vitro gastro-resistant release, and achieved > 85% drug release within 120 min after a pH change to 6.8 during a one-year stability study (25 °C; 60% RH). FTIR-ATR analysis of the CEC internal surface confirmed the temperature-dependent restructuring of hypromellose and E sorption, a phenomenon not observed with C or T, which is likely attributable to physicochemical distinctions. Oral administration of CEC with T-SES1-pellets (0.5 mg/kg) in piglets demonstrated a delayed peak plasma concentration (Cmax 11.67 ng/mL at 9 h) and sustained systemic exposure (AUC 119.8 ng·h/mL). These in-vivo findings substantiate the gastro-protective effect and enhanced intestinal absorption, positioning the pellet/CEC system as a promising strategy for the application of volatile phytotherapeutics in current pharmacotherapy.
PubMed2026
Drug-associated acute pancreatitis in paediatric versus adult reports: a disproportionality analysis using FAERS.
UNLABELLED: While drug-associated acute pancreatitis is proportionally more prevalent in children than adults, age-stratified pharmacovigilance data remain limited. This study analysed paediatric-specific signals to improve recognition and safety. This study aimed to identify drugs associated with acute pancreatitis in children compared with adults and explored age-related differences in patterns using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). A retrospective disproportionality analysis was conducted on 29,349 reports (November 1970-February 2026) from the FAERS. The dataset included 2138 (7.3%) paediatric cases (0-17 years). Suspected active pharmaceutical ingredients (APIs) were identified, and reporting patterns were compared between age groups (chi-squared, reporting odds ratio (ROR), proportional reporting ratio (PRR), multivariate regression analysis). The top ten suspected drugs in children were as follows: methotrexate, pegaspargase, asparaginase, dexamethasone, acetaminophen, prednisone, vincristine sulphate, cytarabine, valproic acid, and mercaptopurine. Paediatric cases were primarily linked to oncologic and immunomodulatory treatments, whereas adult reports were mainly linked to antidiabetic and cardiovascular agents. Seven APIs present in the top 25 list of children and adults (dexamethasone, acetaminophen, prednisone, tacrolimus, lamivudine, didanosine, furosemide) showed significantly higher reporting proportions in children (p < 0.01). Dexamethasone, tacrolimus, and didanosine showed positive interaction terms with serious outcomes in adjusted models. Serious outcome and consumer-reporting were more common in neonates and infants. CONCLUSION: Distinct age-dependent patterns were identified. These findings support paediatric-specific pharmacovigilance assessment and caution against direct extrapolation of adult spontaneous-reporting patterns to children. A clinically useful list of drugs with the highest reporting frequencies in children has been generated. WHAT IS KNOWN: • Drug-associated acute pancreatitis is proportionally more prevalent in children. • The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) can be used to analyse and explore age-dependent patterns. WHAT IS NEW: • The top ten suspected drugs in children were as follows: methotrexate, pegaspargase, asparaginase, dexamethasone, acetaminophen, prednisone, vincristine sulphate, cytarabine, valproic acid, and mercaptopurine, linked to oncology and immunomodulation. • Compared to adults, seven drugs (dexamethasone, acetaminophen, prednisone, tacrolimus, lamivudine, didanosine, furosemide) showed significantly higher reporting proportions in children. Dexamethasone, tacrolimus, and didanosine were associated with serious events.
PubMed2026
Medicinal Chemistry of Agents for Cancer Therapy and Diagnosis From Uruguay.
This review summarizes the evolution of our research on anticancer agents, from early efforts on hypoxia-selective cytotoxins to more recent developments in chemoprevention, molecular targeting, and radiopharmacy. Initial studies focused on the design of N-oxide-containing heterocycles as bioreductive-prodrugs activated under tumor hypoxia. While early triazine N-oxides and furoxans showed limited selectivity, these studies underscored the importance of redox-properties in biological activities. This led to the identification of phenazine 5,10-dioxides as a more suitable pharmacophore, affording compounds with improved potency- and hypoxia-selectivity, supported by mechanistic-, physicochemical-, and in vivo studies. Parallel efforts explored metal-based complexes and formulation strategies enhancing bioavailability and therapeutic performance. Alongside these efforts, cancer chemopreventive-agents were investigated, particularly chalcone-derived scaffolds and related hybrids capable of modulating phase I/II enzymes through Nrf2 activation. Additionally, attention has shifted toward targeted- and diagnostic-approaches, including radiopharmaceuticals for hypoxia-imaging and the use of biomolecular recognition systems, such as aptamers, polypeptides, and antibodies, to selectively address tumor-associated biomarkers. These strategies include aptamer-based biotherapeutics for drug delivery and imaging, as well as approaches combining tyrosine kinase receptor targeting with BNCT. Furthermore, bioorthogonal-methodologies have been explored enabling selective in situ activation and targeting. Together, these studies illustrate a multidisciplinary approach integrating chemistry, biology, and pharmacology toward more selective anticancer strategies.
PubMed2026
Pharmacology, Medicinal Chemistry, and Therapeutic Potential of Imidazoline Receptor Ligands.
The imidazoline receptor (IR) system, comprising the I1R, I2R, and I3R subtypes, consists of binding sites involved in cardiovascular, metabolic, and neurological disorders. This review updates the 2004 compilation by Dardonville and Rozas on IR ligands, emphasizing promising ligands, subtype selectivity, and pharmacological profiling. Representative ligands for each subtype are analyzed to highlight key pharmacological aspects, including affinity, selectivity, and functional activity, integrating findings from preclinical and clinical studies. Critical molecular targets such as Nischarin/IRAS for I1R and MAO-B-associated sites for I2R are discussed in the context of ligand design and CNS penetration. I1R-selective ligands, exemplified by rilmenidine, show improved selectivity over α2-adrenoceptors and exhibit antihypertensive, metabolic, and neuroprotective effects. I2R ligands display neuroprotective, anti-inflammatory, and analgesic activities, with CR4056 progressing to Phase II trials. PET imaging with [11C]BU99008 has validated I2R upregulation as a biomarker for neurodegeneration. Overall, the IR system presents therapeutic opportunities: I1R for cardiovascular and metabolic disorders, I2R for pain and neurodegeneration, and I3R for diabetes. Continued ligand optimization and receptor characterization are essential for clinical translation.