Pharmacology Research & Perspectives最新文献

{"title":"Pharmacodynamics of Vancomycin Against Coagulase-Negative Staphylococci Bloodstream Infections.","authors":"Kiera H Harwood, Courtney E Brusamarello, Amanda L Wilkins, Xiao Zhu, Cornelia B Landersdorfer, Amanda Gwee","doi":"10.1002/prp2.70180","DOIUrl":"10.1002/prp2.70180","url":null,"abstract":"<p><p>The recommended therapeutic target for vancomycin for serious methicillin-resistant S. aureus infections is an area under the concentration-time curve (AUC) over 24 h to a minimum inhibitory concentration (MIC) ratio of ≥ 400. Its applicability to coagulase-negative staphylococcal (CoNS) bloodstream infections is unclear. Our review aims to determine the pharmacodynamic target of vancomycin for CoNS bloodstream infections. In January 2025, MEDLINE, Embase, and PubMed were searched to identify manuscripts reporting the relationship between vancomycin drug exposure (AUC) and bactericidal activity or clinical response for CoNS. Studies of alternative drug delivery systems/formulations, combination therapy, prophylaxis, other infections, and static in vitro studies were excluded. Overall, six articles were included. One in vivo study in young infants found that an AUC_0-24 ≥ 300 mg/L·h and AUC₂₄ ≥ 424 mg/L·h were associated with a 7.8-fold and 7.3-fold increased likelihood of bacteriological cure, respectively. Two studies in adults showed that an AUC₂₄/MIC ratio ≥ 373 resulted in improved treatment success and microbiological eradication. An in vitro model demonstrated that a vancomycin AUC₂₄/MIC ratio ≥ 665 achieved maximal bacterial killing, while a rabbit model linked an AUC₂₄/MIC ≥ 520 to an 80% reduction in C-reactive protein. Early treatment within 24 h was associated with the greatest chance of bacteriological cure. Two studies of biofilm-embedded CoNS demonstrated inadequate bacterial killing at AUC₂₄/MIC ratios of 260 and 354. Overall, or CoNS bloodstream infections, an AUC₂₄ ≥ 424 mg/L·h (median MIC 1 mg/L) or AUC₂₄/MIC ≥ 373 improves clinical outcomes. This review highlights the need for early effective vancomycin treatment. Alternative antibiotic therapy should be considered for biofilm-embedded CoNS infections.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 5","pages":"e70180"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186551","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":"The Use of Proton Pump Inhibitors Among Adults in Norway-A Nationwide Drug Utilization Study.","authors":"Reidar Fossmark, Sveinung Molnes, Liv Sagatun, Øyvind Salvesen, Olav Spigset","doi":"10.1002/prp2.70182","DOIUrl":"10.1002/prp2.70182","url":null,"abstract":"<p><p>The use of proton pump inhibitors (PPIs) has increased in Western countries over several decades, and there is concern about unsubstantiated indications and effects of long-term use. The study aimed to describe the prevalence, incidence, indications, and prescription pattern for PPIs over the past decade in an entire national cohort. This nationwide drug utilization study used data from the Norwegian Prescription Database and Norwegian Patient Registry. Patterns of PPI use were investigated from 2009 to 2022. Prevalent, long-term, and incident PPI use were calculated. The indication for PPI was defined by the diagnosis code linked to each prescription. Upper endoscopies during the study period were assessed for incident PPI users. PPI prescription increased from 58.1 mill DDD in 2009 to 166.9 mill DDD in 2022, that is, 43 and 106 DDD/1000 inhabitants/day. Prevalent PPI use increased from 3.5% to 9.9%, paralleling an increased incidence from 2.9% to 5.4%. The dominant indications in 2009 and 2022 were esophageal disease in primary care (72.5% and 57.6% of total DDDs) and GERD in specialist care (10.7% and 4.7% of total DDDs). Musculoskeletal disorders, pain, and ulcer prophylaxis all increased during the period. Upper endoscopy around incident PPI use decreased from 25.3% to 11.1%. In conclusion, the 2.46-fold increase in prevalent PPI use was caused by an absolute increase in PPI prescribed against esophageal disease and GERD, and prophylaxis in patients using ulcerogenic comedication, mainly prescribed in primary care. The findings may help inform strategies to reduce a probable overuse of PPIs.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 5","pages":"e70182"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12483766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200178","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":"Comparative Efficacy and Renal Safety of Entecavir and Tenofovir Disoproxil Fumarate in the Treatment of Chronic Hepatitis B: A Retrospective Cohort Study From Vietnam.","authors":"Thong Duy Vo, Han Ngoc Gia Nguyen, Sang The Phan","doi":"10.1002/prp2.70177","DOIUrl":"10.1002/prp2.70177","url":null,"abstract":"<p><p>Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are first-line antiviral agents for chronic hepatitis B (CHB), yet comparative real-world data in Southeast Asian populations remain limited. This retrospective cohort study aimed to compare the efficacy, biochemical response, antifibrotic effect, and renal safety of TDF versus ETV in treatment-naïve Vietnamese patients with CHB over a 48-week period. A total of 348 patients (TDF: 181; ETV: 167) were included and evaluated at baseline, Weeks 12, 24, and 48. Both groups demonstrated comparable virologic suppression at Week 48 (TDF: 58.0%, ETV: 52.1%, p > 0.05). TDF achieved significantly higher ALT normalization at Week 24 (72.9% vs. 59.9%, p = 0.01) and Week 48 (84.0% vs. 69.5%, p = 0.001). In contrast, ETV led to faster AST normalization and greater early reductions in APRI and FIB-4 at Week 12. Renal function mildly declined in the TDF group (mean eGFR change: -3.84 ± 11.98, p < 0.001) but improved in the ETV group (+3.02 ± 12.34, p = 0.002). Both treatments were well tolerated with no virologic breakthrough or serious adverse events. In conclusion, both TDF and ETV offer effective antiviral therapy for Vietnamese CHB patients. TDF may be preferable in patients with active hepatic inflammation, whereas ETV may benefit those with baseline renal concerns or early fibrotic progression. These findings support a tailored approach to HBV management based on individual patient profiles.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 5","pages":"e70177"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12489984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207148","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":"Safety Monitoring of Colistin Therapy in Critically Ill Neonates With Late-Onset Sepsis: A Retrospective Observational Study.","authors":"Baran Cengiz Arcagok, Akan Yaman, Turkay Rzayev, Nazli Jalalzada, Ibrahim Kandemir, Asli Memisoglu, Hulya Selva Bilgen","doi":"10.1002/prp2.70178","DOIUrl":"10.1002/prp2.70178","url":null,"abstract":"<p><p>This study aimed to evaluate the safety of colistin therapy by monitoring renal function and electrolyte levels in critically ill neonates with late-onset sepsis (LOS) hospitalized in the neonatal intensive care unit (NICU) between 2015 and 2021. This retrospective case-control study included 58 critically ill neonates treated with colistin for late-onset sepsis and 22 control neonates with late-onset sepsis who did not receive colistin. Data were analyzed to compare patient outcomes, microbiological profiles, and side effects of treatment. Statistical analyses were performed using repeated-measures ANOVA and Bayesian calculations to evaluate serum creatinine levels and biochemical parameters over time. Serum creatinine levels showed similar alterations within the first 7 days of colistin treatment with moderate evidence. However, serum magnesium and sodium levels were lower on the 7th day in the colistin-treated group compared with the control group. Colistin therapy in critically ill neonates with late-onset sepsis appears to be a viable treatment option with an acceptable short-term safety profile. These findings emphasize the importance of routine monitoring of renal function and electrolyte levels during colistin use in neonatal intensive care to minimize potential complications.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 5","pages":"e70178"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12483836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200100","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":"No Evidence of QTc Interval Prolongation With Baxdrostat Treatment: Concentration-QTc Modeling Assessment.","authors":"Mikael Sunnåker, Christian Källgren, Joanna Parkinson, Corina Dota, Christer Gottfridsson, David Janzén, Anita Andersson, Glenn Carlson","doi":"10.1002/prp2.70181","DOIUrl":"10.1002/prp2.70181","url":null,"abstract":"<p><p>Baxdrostat is a novel, highly potent, selective, competitive inhibitor of human aldosterone synthase currently under development for the treatment of uncontrolled and resistant hypertension and chronic kidney disease. We assessed the risk of QTc-interval prolongation with baxdrostat using concentration-QTc (C-QTc) modeling in healthy adult participants using data from two placebo-controlled Phase 1 studies: a multiple-ascending dose (MAD) study of baxdrostat 0.5-5 mg (N = 56; NCT05500820) and a Phase 1 four-way crossover thorough QT/QTc (TQT) study assessing the pharmacokinetics, pharmacodynamics, safety and tolerability of baxdrostat at supratherapeutic doses of 16 and 32 mg (N = 28; NCT06194032). In the TQT study, 28 participants were randomized to one of four treatment sequences (each n = 7) of baxdrostat 16 mg, baxdrostat 32 mg, placebo and open-label moxifloxacin 400 mg. Digital electrocardiogram and pharmacokinetic data were collected at baseline and up to 48 h post dose. Dependent and independent variables of the pre-specified linear mixed-effect model were placebo-corrected baseline-adjusted ΔΔQTcF and baxdrostat plasma concentrations, respectively. Results were consistent between the two C-QTc modeling analyses. Baxdrostat treatment did not produce QT-interval prolongation, both at concentrations of interest and geometric mean of the maximum observed plasma concentration. Upper bounds of the two-sided 90% confidence interval for the ΔΔQTcF mean estimates were < 10 ms. Pharmacokinetic data for the 16 and 32 mg doses in the TQT study were as expected, and both doses were well tolerated. These data illustrate that baxdrostat is not associated with the risk of QT-interval prolongation at therapeutic and supra-therapeutic concentrations.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 5","pages":"e70181"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12518165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286633","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":"Sex-Dependent Long-Term Neurobehavioral Recovery in Experimental Neonatal Hypoxic-Ischemic Encephalopathy.","authors":"Elisa Landucci, Bruno P Imbimbo, Alessia Melani, Domenico E Pellegrini-Giampietro, Fabrizio Facchinetti","doi":"10.1002/prp2.70183","DOIUrl":"10.1002/prp2.70183","url":null,"abstract":"<p><p>This study investigates the sex-dependent effects of therapeutic hypothermia and a neuroprotectant (CHF6467) on long-term neurobehavioral recovery in neonatal rats subjected to hypoxic-ischemic encephalopathy. Using the Rice-Vannucci model, rats were divided into five groups: sham lesion, hypoxic-ischemic insult, hypoxic-ischemic insult with CHF6467, hypoxic-ischemic insult with hypothermia, and hypoxic-ischemic insult with CHF6467 combined with hypothermia. Behavioral tests at postnatal day 30 (P30) and 60 (P60) revealed significant improvements in motor coordination and spatial memory in treated groups compared to the vehicle-treated group, associated with reductions in infarct size at P60. Notably, female rats exhibited superior motor coordination recovery compared to males, despite similar neuroprotection levels. This suggests that motor coordination recovery is not solely dependent on the extent of neuronal damage. Conversely, spatial memory impairment was sex-independent and closely associated with the degree of neuroprotection. These findings highlight the importance of considering sex differences in neuroprotective treatment efficacy and suggest potential variations in responses between males and females in clinical settings.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 5","pages":"e70183"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12485222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200078","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":"Preclinical Evaluation of a Novel Molecule Targeting Nucleoside Homeostasis to Restore Energy Metabolism and Cognitive Function in Alzheimer's Disease.","authors":"Kuo-Chen Wu, Chien-Yu Lin, Thanh Tran, Jung-Hsing Lin, Hsin-Hsien Yeh, Chin-Jui Ho, Yijuang Chern, Chun-Jung Lin","doi":"10.1002/prp2.70176","DOIUrl":"10.1002/prp2.70176","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the most prevalent cause of dementia, characterized by progressive cognitive decline and cerebral metabolic impairment. Yet, the therapeutic options for addressing the disease pathogenesis are limited. Here, we report an approach by targeting brain nucleoside homeostasis and energy metabolism to alleviate AD-associated cognitive deficits. A compound, J4, was designed to modulate nucleoside homeostasis by interacting with the equilibrative nucleoside transporter-1 (ENT1). The effects of J4 on brain nucleoside homeostasis and energy metabolism were examined in mice. Two AD animal models, THY-Tau22 and APP/PS1 mice, were used to evaluate the translational potential of J4 for the treatment of AD. Cognitive function and functional ability were assessed using the Morris water maze, Y-maze, and nesting behavior tests. The pharmacodynamic marker was explored, and the pharmacokinetic and safety properties of J4 were evaluated. As a result, being administered after disease onset, oral J4 administration rescued memory and cognitive dysfunction in both tau and amyloid AD mouse models. Metabolomic analysis showed that J4 increased brain nucleoside levels and facilitated brain primary metabolism, including glucose metabolism and the pentose phosphate pathway. The [¹⁸F]-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging further demonstrated that glucose metabolism can be used as a pharmacodynamic biomarker for the target engagement of J4 on ENT1. The nonclinical studies also demonstrated the ideal pharmacokinetic and safety profiles of J4, supporting that targeting nucleoside homeostasis can improve brain energy metabolism and is a promising approach for AD treatment.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 5","pages":"e70176"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12496225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An In Vitro Calibration Model for Vancomycin Quantification in Brain Extracellular Fluid: Toward Improved Dosing in Postoperative Infections.","authors":"Skaistė Žukaitienė, Ainė Žygaitė, Gabrielė Milkintaitė, Jolita Pancerė, Neringa Balčiūnienė, Astra Vitkauskienė, Romaldas Mačiulaitis","doi":"10.1002/prp2.70179","DOIUrl":"10.1002/prp2.70179","url":null,"abstract":"<p><p>Postoperative central nervous system (CNS) infections are associated with high mortality and present a therapeutic challenge due to limited antibiotic penetration into the brain extracellular fluid (ECF). Vancomycin, frequently used in this setting, requires therapeutic drug monitoring; however, its quantification in brain ECF via microdialysis is limited by the need for accurate calibration of relative recovery (RR). This study aimed to determine the in vitro RR of vancomycin under conditions simulating clinical neuromonitoring to support application in clinical practice. Vancomycin RR was assessed using forward dialysis and retrodialysis techniques at a fixed perfusion rate of 0.3 μL/min, consistent with standard neuromonitoring protocols. Vancomycin concentrations were measured using a homogeneous enzyme immunoassay across subtherapeutic, therapeutic, and supratherapeutic levels. RR was calculated as the ratio of microdialysate to reference solution concentrations. Mean RR was 86.5% (SD 3.6%) for forward dialysis and 86.4% (SD 2.1%) for retrodialysis, with no significant difference between techniques (p = 0.957). RR remained consistent across all tested concentration levels (p = 0.051). A strong correlation was observed between vancomycin concentrations in the microdialysate and the study solution (r = 0.997, p < 0.001). The high and stable RR achieved under clinically relevant conditions supports the use of this in vitro microdialysis model as a reliable calibration tool. This model may aid in estimating vancomycin concentrations in brain fluid, facilitating dose optimization in patients undergoing microdialysis-based monitoring for postoperative CNS infections.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 5","pages":"e70179"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12519522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286694","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":"Interrogating the Perceptions of Undergraduate Pharmacology Teaching on an MBBS Programme at a UK Medical School.","authors":"Eleanor Renee Smith, Maximilian Paley, Raji Kaur Lalli, Maryam Malekigorji, John Broad","doi":"10.1002/prp2.70136","DOIUrl":"10.1002/prp2.70136","url":null,"abstract":"<p><p>Pharmacology education at medical schools in the UK aims to give newly qualified doctors the ability to apply foundational knowledge of pharmacology and to be able to prescribe drugs safely. This study aimed to assess a current pharmacology curriculum and understand the perspectives of both students and educators around pharmacology teaching. Employing a mixed-methods approach, the research utilized documentation analysis, focus groups, semi-structured interviews, and online questionnaires with students, educators and senior academic tutors. The analysis of the current curriculum revealed that 1069 drugs or drug classes were introduced to students in their first 2 years of study of drugs and drug classes. Students reported feeling overwhelmed with the number of drugs they were expected to learn. They suggested increasing contextual learning experiences and more practical prescribing experience. Students emphasized the need for greater visibility of pharmacology teaching. Students and educators identified challenges in integrating pharmacology effectively, which contributed to knowledge gaps. Disparities between students' perceptions of pharmacology education and educators' confidence in its delivery were found. These findings suggest the need to address the number of drugs introduced to students in their first 2 years of study. Recommendations include reducing the number of drugs or drug classes introduced to students, highlighting important drugs or classes, enhancing the visibility of pharmacology in the curriculum, and educating and supporting staff when preparing teaching sessions that involve pharmacology. These measures may address students' feelings of being overwhelmed by pharmacology, aligning with the aim of developing medical students into safe prescribers following graduation.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 4","pages":"e70136"},"PeriodicalIF":2.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718307","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":"A Unified Explanation for Drug Repurposing and Pharmacological Pleiotropy Based on Classical and Statistical Thermodynamics.","authors":"Richard Head, Saiful Islam, Jennifer H Martin","doi":"10.1002/prp2.70158","DOIUrl":"10.1002/prp2.70158","url":null,"abstract":"<p><p>Drug repurposing is an authentic, emerging, and growing aspect of drug development when the demand for new therapeutic solutions is high. Many repurposed drugs have been discovered by serendipity or a non-ordered process driven by chance and sharp observation. These discoveries provide strong evidence for the existence of pharmacological pleiotropy, a highly ordered process well described by thermodynamics. Pleiotropy is an efficient way of propagating information and maintaining the specificity of a biological message and has been a cornerstone in genetics research over decades. While the definition, scale, diversity, and complexity associated with drug repurposing are well documented, pharmaceutical pleiotropy that is fundamental to our understanding of drug repurposing remains less explored. In this review, we examine pharmacological pleiotropy and its underpinning thermodynamics in drug repurposing. Additionally, we have drawn upon the universality of thermodynamics to provide insights into pharmaceutical pleiotropy. We suggest that, in serendipitous drug discovery, information in the repurposed drug often exceeds what was thought available with the rational design of the drug. Our interest in repurposing is on leveraging this information and knowledge generally once a therapeutic benefit from a new chemical entity (NCE) has been demonstrated. This requires a different process from standard drug discovery, and this repurposed pathway is the focus of our manuscript. In this review, we propose that drug repurposing can be defined using Information theory (Shannon entropy), Boltzmann statistical entropy, and the thermodynamic principles for spontaneity described by Gibbs free energy of binding. We conclude that therapeutics including repurposed drugs are facilitators of information and instructional transfer and that the distinguishing features of pharmacology, Information theory, and statistical mechanics are intimately linked. With advances in artificial intelligence and machine learning, with their strong links to Information theory and statistical mechanics, now is an appropriate time to further explore these relationships.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 4","pages":"e70158"},"PeriodicalIF":2.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732709","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}