Saudi Pharmaceutical Journal最新文献

{"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}

{"title":"Towards standardized skin testing for drug-induced allergic reactions.","authors":"Moneerah AlGassim, Fatimah Alawami, Ghalia H Bakhsh, Samia Al-Shouli, Nada K Alhumaid, Abdullah A Alshehri, Fahad A Almughem, Yahya M K Tawfik, Rawan Fitaihi, Nasser D Aljohani, Abdullah O Alshehry, Essam A Tawfik","doi":"10.1007/s44446-025-00031-5","DOIUrl":"10.1007/s44446-025-00031-5","url":null,"abstract":"<p><p>Standardization of skin tests is essential for detecting allergen sensitization, confirming diagnoses, and guiding treatment of allergen-induced conditions. The rise in drug-induced reactions presents a challenge to healthcare practitioners, as incomplete or inaccurate drug allergy histories can compromise patient safety and result in medication errors. Drug hypersensitivity reactions (DHR) are akin to allergic responses, triggered by either the active ingredient or excipients in a drug. Distinguishing between a drug allergic reaction and a predictable adverse drug reaction (ADR) is vital in clinical practice. Cutaneous testing, a common diagnostic modality, uses non-irritant drug concentrations, tested and validated for key drug classes. This article collects up-to-date concentrations, serving as a reference for healthcare practitioners. These concentrations vary but are generally prepared by dissolving the commercial form of the drug's tablet or capsule content in normal saline, white petrolatum, or sterile water for irrigation. However, the lack of data and standardized protocols on optimal non-irritant drug concentrations for oral dosage forms has led to variability in these tests' sensitivity, specificity, and performance.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 4","pages":"26"},"PeriodicalIF":3.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592723","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":"Engineering stable Amlodipine suspensions for flexible compounding at King Khaled University Hospital.","authors":"Ehab Elzayat, Hadyah F Alotaibi, Mohamed H Al-Agamy, Lama A Alharabi, Mohammed R Alhuzani","doi":"10.1007/s44446-025-00028-0","DOIUrl":"10.1007/s44446-025-00028-0","url":null,"abstract":"<p><p>Extemporaneous liquid formulations are crucial for patients unable to swallow solid dosage forms. While the United States Pharmacopeia (USP) recommends a 3-month beyond-use date for extemporaneous Amlodipine suspensions, uncertainties persist regarding the impact of active pharmaceutical ingredient (API) source variability, the confirmation of extended in-use stability, and the practical challenges of adapting formulations to local market raw material availability. This study aimed to address these gaps by investigating the physicochemical and microbiological stability of extemporaneous Amlodipine suspensions prepared from different API sources and stored under simulated in-use and closed conditions for 3 months. Eight formulations were prepared using different dosage forms (tablets or capsules), manufacturers (brand or generic), strengths (5 mg or 10 mg), and storage conditions. Physical stability was assessed via organoleptic properties and pH measurements, chemical stability via a validated ultra-performance liquid chromatography-ultraviolet method, and microbiological stability through total aerobic microbial count and total yeast and mold count. All formulations demonstrated stability over 3 months at 5°C, with drug content maintained (mean 103.94% ± 1.79 SD, range 101.79-107%) of the initial concentration and no microbial growth detected, even under in-use conditions. No significant differences were observed between tablet- and capsule-based preparations. These findings confirm the United States Pharmacopeia's 3-month beyond-use date recommendation and highlight the potential for more flexible preparation methods, including alternatives required by local market shortages. Our findings also support a 3-month in-use stability, which could improve patient convenience, reduce medication waste, and provide a more sustainable compounding approach at King Khaled University Hospital.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 4","pages":"23"},"PeriodicalIF":3.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585475","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":"Facile indazole-endowed thiadiazole hybrid derivatives as antibacterial, anti-diabetic and thymidine phosphorylase inhibitors: An insight to experimental, in-vitro biological potential and computational approaches.","authors":"Sabeen Arshad, Aneela Maalik, Wajid Rehman, Yousaf Khan, Mohammed M Alanazi, Hina Sarfraz, Liaqat Rasheed","doi":"10.1007/s44446-025-00003-9","DOIUrl":"10.1007/s44446-025-00003-9","url":null,"abstract":"<p><p>In this study, a series of newly synthesized indazole-based thiadiazole hybrid derivatives (1-13) were successfully synthesized from indazole-based thiosemicarbazides starting from the 5-methyl-1H-indazole-3-carboxylic acid. The structure of the synthesized compounds were confirmed through different spectroscopic techniques i.e. FT-IR, ¹HNMR, ¹³CNMR and HRMS. Furthermore, the biological potency of the synthesized indazole based thiadiazole scaffolds were assessed through in-vitro screening against thymidine phosphorylase and α-glucosidase enzymes. The biological potential of the synthesized derivatives was found to be influenced by the size, nature and position of substituents on the hybrid scaffold. Some derivatives displayed significant inhibitory activity, with some exhibiting superior potency compared to standard reference drugs. Moreover, the inhibitory potential of the derivatives were compared with standard 7-Deazaxanthine (7DX) and acarbose. Notably, derivatives 1, 2, 3, 5, 7, and 8 demonstrated remarkable inhibitory activity against thymidine phosphorylase and α-glucosidase, respectively. In addition, based on docking studies, the synthesized indazole-based thiadiazole scaffolds showed good binding interactions with different amino acids. Comparing the analogs' binding affinities and molecular interactions with standard reference drugs revealed favorable mechanisms. Similarly, an ADMET analysis was performed on the synthesized derivatives in order to predict their pharmacokinetics and drug-like characteristics. Using ADMET profiler, it was determined that the derivatives possessed drug-like properties. As a result of this study, indazole based thiadiazole hybrid derivatives have been designed, synthesized, and biologically evaluated as potent dual inhibitors of thymidine phosphorylase and α-glucosidase. These scaffolds display significant inhibitory potential, which were further analysed by docking and ADMET studies, emphasizing their potential as potent compounds for the development of new therapeutic agents that target these enzymes.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 4","pages":"20"},"PeriodicalIF":3.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585400","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":"Excipients in pharmaceuticals: mechanisms of hypersensitivity and the role of global pharmacovigilance.","authors":"Ruba Malkawi, Lora Altahrawi","doi":"10.1007/s44446-025-00004-8","DOIUrl":"10.1007/s44446-025-00004-8","url":null,"abstract":"<p><p>Excipients are important inactive components in drug formulations that ensure stability, bioavailability, and patient compliance. However, emerging evidence suggests that certain excipients, once considered inert, can cause hypersensitivity reactions in certain individuals. Such reactions include mild erythema due to systemic anaphylaxis and create clinical challenges that are difficult to handle. This review presents a systematic review of the existing literature on excipient hypersensitivity, with specific attention paid to commonly implicated excipients such as polyethylene glycol (PEG), parabens, and tartrazine. Hypersensitivity mechanisms (immune-mediated [IgE, T-cell] and non-immune) are discussed, along with their clinical features and diagnostic challenges. In addition, geographic variations in reporting are discussed, which in turn focus on the role of pharmacovigilance in the reduction of risk. Geographic variations in excipient hypersensitivity reporting are also discussed, highlighting disparities in pharmacovigilance efforts across different regions. This review also discusses recent work, regulatory issues, and desensitization protocols for the control of hypersensitivity reactions. Persistent surveillance and individual strategies are needed to enhance patient safety in the context of excipient-induced hypersensitivity.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 4","pages":"18"},"PeriodicalIF":3.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12237841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585477","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}