Saudi Pharmaceutical Journal最新文献

{"title":"GLP-1 receptor agonism: a transformative approach for managing type-2 diabetes and obesity.","authors":"Abdulrahman G Alharbi","doi":"10.1007/s44446-025-00038-y","DOIUrl":"10.1007/s44446-025-00038-y","url":null,"abstract":"<p><p>GLP-1 receptor agonists represent a breakthrough for managing type-2 diabetes and obesity, offering metabolic benefits across multiple organ systems. These medications provide effective glycaemic control, significant weight reduction, and cardiovascular protection through complex signalling pathways affecting pancreatic, gastrointestinal, neural, and cardiovascular tissues. Their therapeutic potential extends beyond metabolic disorders. Clinical studies demonstrate substantial decreases in HbA1c, body weight (15-20%), and cardiovascular events compared to traditional treatments. Emerging applications include non-alcoholic fatty liver disease and neurodegenerative conditions. Significant barriers still exist despite established safety profiles, such as high costs that restrict access worldwide, a lack of predictive biomarkers for treatment response, a lack of knowledge about the mechanistics of gut microbiota interactions, and an incomplete understanding of long-term safety, particularly with regard to thyroid and pancreatic effects. Research gaps include appropriate patient classification, cost-effectiveness across healthcare systems, and established methodologies for developing applications. Potential future developments include novel delivery mechanisms, multi-receptor agonists, and a broader range of therapeutic uses for the treatment of metabolic disorders and their consequences. From their identification as incretin hormones to development of long-acting analogue, GLP-1 agonists have revolutionized metabolic disease management. Their pleiotropic benefits arise from intricate signalling cascades that regulate appetite, insulin secretion, and energy homeostasis across multiple tissues.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 5","pages":"34"},"PeriodicalIF":4.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-coding RNA-mediated gene regulation in Alzheimer's disease pathogenesis: molecular insights and emerging innovations.","authors":"Sami I Alzarea","doi":"10.1007/s44446-025-00026-2","DOIUrl":"10.1007/s44446-025-00026-2","url":null,"abstract":"<p><p>The accumulation of pathological markers, such as tau tangles and amyloid-beta (Aβ) plaques, and progressive cognitive dysfunction are the markers of Alzheimer's disease (AD). The development of successful therapeutic plans requires exposure to the molecular mechanisms underlying AD development. The importance of non-coding RNAs (ncRNAs), such as circular RNAs (circRNAs), microRNAs (miRNAs), long ncRNAs (lncRNAs), and PIWI-interacting RNAs (piRNAs), in controlling gene expression and influencing the pathophysiology of disease has been brought to light by recent studies. With a focus on their role in important processes such tau hyperphosphorylation, neuroinflammation, and amyloid-beta formation, this study attempts to give a thorough overview of the several types of ncRNAs and their dysregulation in AD. The genetic variants that are associated with the function of ncRNA including single nucleotide polymorphisms (SNPs) may influence ncRNA expression and activity, thereby impacting the susceptibility of individual towards AD. Furthermore, the impact of biomarkers of ncRNAs for early diagnosis and therapeutic option for intervention, highlighting most recent advancement in high-throughput technologies and bioinformatics facilitating ncRNA profiling has also being discussed. The integration of multi-omics approaches and artificial intelligence, new advancement for the complex relationship among ncRNAs and AD pathology are also discussed. The enhancement and understanding of ncRNAs could lead to the door for novel therapeutic concepts for the mitigation of AD progression, offering effective interventions in a disease that currently starves the curative treatments.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 5","pages":"33"},"PeriodicalIF":4.3,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12454739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spontaneous adverse drug reaction reporting: potential facilitators perceived by community pharmacists in Egypt - a cross-sectional study.","authors":"Mohamed Bahlol, Mary Bushell, Hani M J Khojah, Rebecca Susan Dewey","doi":"10.1007/s44446-025-00025-3","DOIUrl":"10.1007/s44446-025-00025-3","url":null,"abstract":"<p><p>Pharmacists are recognized as specialists in medications and are responsible for maintaining drug safety. A recent study showed that Egyptian community pharmacists face several barriers to the spontaneous reporting of adverse drug reactions (ADRs). This study aimed to identify the potential facilitators perceived by community pharmacists in Egypt that could enhance ADR reporting and contribute to the development of national ADR data. A cross-sectional survey was conducted using a self-administered questionnaire distributed to 1,316 community pharmacists in Egypt. Of the 905 respondents (68.7% response rate), only 125 (13.8%) revealed they had reported an ADR, with 30 (24.4%) being unable to correctly identify ADR types and 34 (27.2%) reporting they lacked the training required to do so. Key facilitators identified be respondents included ensuring that ADR-related training is available from universities (95.7%), the Egyptian Pharmacists Syndicate (91.9%), and peer-reviewed journal articles (90.6%). Participants advocated for simplifying the reporting process (92.5%), providing clear instructions (92.8%), having access to a smartphone application (80.0%), receiving regular reminders (92.4%) having their role promoted in the media (95.6%). Community pharmacists are crucial in ADR reporting, especially in low-to-middle-income countries e.g. Egypt. The study identified several facilitators to improve reporting practices, including educational interventions, process enhancements, and motivational strategies. Implementing these facilitators could address underreporting and data inaccuracies.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 5","pages":"32"},"PeriodicalIF":4.3,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12454801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Talazoparib and radiation enhance the senolytic efficacy of venetoclax in therapy-induced senescent triple-negative breast cancer cells.","authors":"Sultan Almudimeegh, Mashal M Almutairi, Abrar Softah, Khalid Alhazzani, Lama Binobaid, Musaad Alshammari, Homood M As Sobeai, Tareq Saleh, Moureq R Alotaibi, Ali Alhoshani","doi":"10.1007/s44446-025-00034-2","DOIUrl":"10.1007/s44446-025-00034-2","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) presents ongoing clinical challenges, often leading to relapse in many patients. The relapse is partly explained by tumor cells transitioning into a senescent state following chemotherapy or radiation, resulting in a more aggressive phenotype, contributing to disease recurrence. Consequently, combining senolytics with traditional treatments could be a viable and promising strategy in treating TNBC. To address this, we induced therapy-induced senescence (TIS) both in vitro and in vivo by combining the poly ADP-ribose polymerase (PARP) inhibitor talazoparib with radiation. We tested whether exposure to the senolytic agent, venetoclax, would result in the eradication of senescent cells and augmentation of apoptosis. TIS Markers, like senescence-associated beta-galactosidase (SA-β-gal), CDKN1A, and senescence-associated secretory phenotype (SASP) marker IL-6, were altered following talazoparib and radiation in both 4T1 and MDA-MB-231 TNBC cell lines. Interestingly, venetoclax treatment following TIS induction led to pronounced apoptotic cell death and significant changes in SA-β-gal and IL-6, implying enhanced sensitivity post-senescence induction. Furthermore, these data were validated in vivo in an immunocompetent TNBC-bearing mouse model, in which venetoclax alone had a modest effect on growth inhibition. However, when combined with radiotherapy/talazoparib, venetoclax dramatically interfered with tumor recovery post-senescence induction, indicating a potential strategy to mitigate disease recurrence. These results suggest that combining radiotherapy with PARP inhibitors with senolytic agents such as venetoclax could potentially overcome disease relapse associated with TNBC.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 5","pages":"31"},"PeriodicalIF":3.4,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12380664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144976182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of CYP3A4 and CYP3A5 polymorphisms on tacrolimus dose requirements in Saudi kidney transplant patients.","authors":"Marzog S Al Nasser, Mai A Alim A Sattar Ahmad, Sherif Edris, Ezz Abdelfattah, Ahmed S Ali, Mohammad F Zaitoun, Futoon H Alharbi, Hadiah B Al Mahdi, Zoheir Damanhouri","doi":"10.1007/s44446-025-00035-1","DOIUrl":"10.1007/s44446-025-00035-1","url":null,"abstract":"<p><strong>Background: </strong>Limited research has explored the genetic variability of CYP3A4 and CYP3A5 in the Saudi population, particularly concerning tacrolimus (Tac) therapy among Saudi kidney transplant patients (SKTP).</p><p><strong>Objectives: </strong>To investigate specific CYP3A4 and CYP3A5 polymorphisms in SKTP and evaluate their influence on Tac dose requirements and trough levels.</p><p><strong>Methods: </strong>A total of 251 Saudi participants were recruited, comprising 129 kidney transplant patients and 122 healthy volunteers. Genomic DNA was extracted, and polymorphisms in CYP3A4 (*1B, *6, *18, *22) and CYP3A5 (*2, *3, *4) were analyzed using real-time PCR and allele-specific sequencing. Genotype frequencies and minor allele frequencies (MAF) were calculated, and the impact of CYP3A variants on Tac dosing and trough levels (C0) was assessed in SKTP.</p><p><strong>Results: </strong>The CYP3A41B polymorphism was absent, with all participants being homozygous wild type (G/G). For CYP3A5*3, 98.4% of participants carried the mutant genotype (*3/*3), while 1.6% carried the wild-type genotype (*1/*1). Patients with the wild-type allele (*1/*1) required significantly higher Tac doses and exhibited lower trough concentrations (C0) compared to those with the mutant genotype (*3/3). Other polymorphisms, such as CYP3A4*22, were rare, with approximately 90% of participants carrying the wild-type allele.</p><p><strong>Conclusion: </strong>This study highlights the high prevalence of the CYP3A5*3/*3 genotype and wild-type CYP3A4 alleles in the Saudi population. The genetic variability significantly affects Tac trough levels and dosing requirements necessary to achieve therapeutic targets. These findings underscore the importance of pharmacogeneticguided Tac dosing to optimize therapeutic outcomes in SKTP.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 5","pages":"30"},"PeriodicalIF":3.4,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144976235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence, toxin virulence genes and investigating the effect of mutations in the tetracycline gene (tetK) on the response of methicillin-resistant Staphylococcus aureus to antibiotics: a study in sickle cell disease patients in Riyadh, Saudi Arabia.","authors":"Adel A Abdulmanea, Naiyf S Alharbi, Mohamed A Farraga, Ali M Somily, Osamah T Khojah, Farjah H Algahtani, Ahmed S Alobaidia, Shine Kadaikunnana, Jamal M Khaled","doi":"10.1007/s44446-025-00033-3","DOIUrl":"10.1007/s44446-025-00033-3","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen associated with antimicrobial resistance, particularly in bloodstream infections affecting individuals with underlying conditions such as sickle cell disease (SCD). Resistance to tetracycline and erythromycin in MRSA is often mediated by efflux pump genes, including tetK, tetM, ermA, and ermC. These genes play a crucial role in reducing the efficacy of commonly used antibiotics, posing significant challenges in clinical management. Understanding the genetic variations within these resistance genes and their association with phenotypic resistance patterns is essential for guiding effective treatment strategies and improving patient outcomes. However, earlier research has not thoroughly examined how changes in the genes tetK, tetM, ermA, and ermC relate to the antibiotic resistance seen in MRSA strains taken from SCD patients. This gap indicates that there must be a focused investigation to bridge the current knowledge deficit and support the development of more targeted therapeutic approaches. This study aimed to investigate the prevalence and genetic basis of antibiotic resistance in MRSA bloodstream isolates from sickle cell disease patients in Riyadh, Saudi Arabia. It looked at the resistance genes, like tetK, ermA, and ermC, and studied how changes in their sequences affected them using evolutionary and structural analysis over seven years. MRSA isolates (n = 34) were obtained from 3,979 SCD patients (2017-2024). Representative strains were analyzed for their antibiotic susceptibility using the VITEK 2 system and PCR-based identification of resistance genes (e.g., tetK, tetM, ermA, and ermC). Among SCD patients, 0.9% exhibited MRSA bloodstream infections, predominantly affecting individuals over 20 years of age. During our study, we made an intriguing discovery that the toxin genes (hlg, hla, Pvl, and sea) were predominant in the MRSA isolates. Sequencing of tetK, ermA, ermC, and 16S rRNA genes was performed, and variations were analyzed using bioinformatics tools (BLAST, MEGA X, CARD, BLASTX). Phylogenetic analysis was conducted, and the results were correlated with phenotypic resistance profiles. All isolates were resistant to β-lactam antibiotics but sensitive to vancomycin and tobramycin. The analysis of the genetic sequence revealed important changes in the tetK gene, with strain RHD-KSA30 exhibiting several different amino acids. Phylogenetic analysis grouped Riyadh strains into distinct clusters. Variations in tetK correlated with differential susceptibility to antibiotics like erythromycin, clindamycin, and ciprofloxacin. The genetic diversity of the tetK gene in MRSA strains and its function in mediating antibiotic resistance are highlighted in this study. Although vancomycin and tobramycin are still effective treatments, the resistance to other antibiotics shows the need for continuous monitoring and the development of tailored treatment plans, especially fo","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 5","pages":"29"},"PeriodicalIF":3.4,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144976246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neomycin sulfate and triamcinolone acetonide suspended ointment designed for transdermal delivery: formulation and in vitro evaluation.","authors":"Jiong Wu, Qian Tang, Xufei Zhao, Yan Shen, Ruixi Liao, Hongxiu Zhang, XiuJuan Feng, Aiping Shi","doi":"10.1007/s44446-025-00027-1","DOIUrl":"10.1007/s44446-025-00027-1","url":null,"abstract":"<p><p>Neurodermatitis and chronic eczema are characterized by severe itching and can lead to complications such as skin infections and folliculitis. Current treatment primarily involves glucocorticoid analogs which may be associated with side effects and lack of effective delivery strategies. The suspended ointment developed in this study aims to address these issues, offering improved therapeutic outcomes. The present study aimed to investigate the relationship between formulation/process variables versus the content uniformity and viscosity of neomycin sulfate and triamcinolone acetonide ointments and to explore the feasibility of using an in vitro approach to assess product sameness. Monofactor analysis was used to evaluate the impact of formulation and process variables. The new formulation was evaluated in terms of the prescription process, quality, stability, in vitro drug release behavior, and distribution of skin. The optimal prescription composition was 0.54% neomycin sulfate, 0.10% triamcinolone acetonide, 5.08% substrate A and 94.28% liquid paraffin. Quality and stability assessments confirmed that the formulation met the required standards for appearance and composition. Mathematical modeling of the drug release profile indicated that the release kinetics evaluated using the vertical diffusion cell method, closely aligned with first-order kinetics. Raman spectroscopy confirmed the successful penetration of triamcinolone acetonide into the skin, triamcinolone acetonide works primarily in the skin. Furthermore, skin irritation tests demonstrated that the formulation caused no detectable irritation. These results demonstrate that it can be a promising drug in treating neurodermatitis and chronic eczema.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 4","pages":"28"},"PeriodicalIF":3.4,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and factors associated with potentially inappropriate medications in elderly stroke patients: A comparison of Beers 2019 and 2023 criteria.","authors":"Xiaofang Tan, Xiaoqun Lv, Weigen Xiong, Yujuan Liu, Ning Zhang","doi":"10.1007/s44446-025-00029-z","DOIUrl":"10.1007/s44446-025-00029-z","url":null,"abstract":"<p><strong>Background: </strong>Polypharmacy is widespread among older adults with ischemic stroke (IS), which may increase the prevalence of potentially inappropriate medications (PIMs). This study aimed to determine the prevalence and factors associated with PIMs in hospitalized IS patients using the 2019 and 2023 Beers criteria.</p><p><strong>Method: </strong>We conducted a cross-sectional study by extracting electronic medical records of hospitalized elderly IS patients (aged ≥ 65 years) at Jinshan Hospital of Fudan University from January to December 2021. PIMs were identified based on the 2019 and 2023 Beers criteria. The coherence of the two criteria was evaluated via the kappa test. Poisson regression was performed to identify factors associated with PIM use.</p><p><strong>Results: </strong>A total of 559 elderly IS patients were included in the study. According to the 2023 Beers criteria, 43.29% of patients used at least one PIM, compared with 38.82% based on the 2019 Beers criteria. The three most frequently identified PIM classes in both versions were antipsychotics, diuretics, and antidepressants. The kappa value was 0.908 (P < 0.001), indicating strong coherence between the two criteria. Female sex, a higher number of prescribed medications, and longer hospital stays were significantly associated with increased PIM use. Across both sets of criteria, the number of prescribed medications was identified as the strongest factor associated with PIM use.</p><p><strong>Conclusion: </strong>The overall prevalence of PIMs was slightly higher according to the 2023 Beers criteria than the 2019 version. PIM use was more prevalent among older female IS inpatients with excessive polypharmacy and hospital stays of 21 days or longer.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 4","pages":"27"},"PeriodicalIF":3.4,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12246315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical features and mortality risk in Acute Ischemic Stroke with COVID-19: a multicenter-based comparative analysis of elderly and younger populations in Saudi Arabia.","authors":"Daniyah A Almarghalani, Mohammad S Alzahrani, Faisal F Alamri, Alqassem Y Hakami, Ahmed I Fathelrahman","doi":"10.1007/s44446-025-00030-6","DOIUrl":"10.1007/s44446-025-00030-6","url":null,"abstract":"<p><p>Ischemic stroke, a major cause of morbidity and mortality in elderly individuals, has increased with coronavirus disease 2019 (COVID-19). This study compared the demographic and clinical features of ischemic stroke patients with COVID-19 aged < 65 years and those aged ≥ 65 years and focused on the impact of comorbidities on mortality. A total of 111 ischemic stroke patients with COVID-19 were investigated. The participants were divided into two age groups: those < 65 years and those ≥ 65 years. Demographic and clinical data were analyzed, and outcomes were compared between age groups. Multivariate logistic regression analysis was used to determine the key factors associated with mortality. Most patients were male (62.2%), with a greater proportion of patients aged ≥ 65 years (70.6% vs. 48.9%, p = 0.021). Hypertension (67.6%), diabetes mellitus (62.2%), and dyslipidemia (34.2%) were prevalent, with dyslipidemia being more common in those aged ≥ 65 years (42.7% vs. 20.9%, p = 0.019). Overall mortality was 23.4%, with no significant difference according to age group (p = 0.341). Multivariate analysis revealed that a 5-year increase in age was a significant predictor of mortality, with an aOR of 1.43 (95% CI: 1.11-1.85), p = 0.006. Males were associated with lower odds of mortality, with an aOR of 0.19 (0.04-0.81), p = 0.025. Dementia and pneumonia were significant predictors of mortality, with aORs of 15.34 (95% CI: 2.72-86.59), p = 0.002 and 11.92 (95% CI: 2.43-58.43), p = 0.002, respectively. These findings highlight age, sex, and specific comorbidities as critical determinants of mortality in this population, emphasizing the need for tailored interventions to address respiratory and cognitive complications alongside traditional risk factors.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 4","pages":"25"},"PeriodicalIF":3.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Mechanistic Physiologically Based Pharmacokinetic (PBPK) modeling approach for fexofenadine: predictive pharmacokinetic insights in humans.","authors":"Maryam Batool, Ammara Zamir, Hussain Alqhtani, Hamid Saeed, Muhammad Fawad Rasool","doi":"10.1007/s44446-025-00024-4","DOIUrl":"10.1007/s44446-025-00024-4","url":null,"abstract":"<p><p>The physiologically based pharmacokinetic (PBPK) modeling is an in-silico technique that determines drug pharmacokinetics (PK) by considering blood circulation and tissue composition within the body. Fexofenadine is an H₁ receptor antagonist drug recommended for treating seasonal allergic rhinitis and chronic idiopathic urticaria. This study aimed to build a PBPK model of fexofenadine to predict its systemic exposure in healthy, diseased, and pediatric populations. The modeling process commenced with a meticulous literature review to collect pertinent PK data on fexofenadine, which was then consolidated into the PK-Sim simulator to develop a drug-specific model in the healthy population. The model was then extrapolated to patients with chronic kidney disease (CKD) and pediatrics by employing disease and age-related physiological variations. Visual predictive checks were executed to substantiate the model's accuracy, along with the computation of observed-to-predicted ratios (R_Obs/Pre), average fold error (AFE), and absolute average fold error (AAFE). The developed PBPK model successfully predicted fexofenadine's PK with AFE values of 0.98, 0.58, and 1.21 for CL/F in healthy, diseased, and pediatric populations, which were confined within a two-fold error range. Furthermore, box-and-whisker plots were generated to critically analyze drug concentration at varying stages of CKD. The presented model offers indispensable insights that may assist clinicians in determining dosing strategies in patients with kidney disease.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 4","pages":"24"},"PeriodicalIF":3.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}