Saudi Pharmaceutical Journal最新文献

Erlotinib (ERL) and Gefitinib (GEF) are weakly basic drugs with pH-dependent solubility profiles mainly dependent on stomach pH. We proposed possible drug and/or food-drug interactions with acidifying agents. Citric acid (CA) and phosphoric acid (PPA) are the most common acidifying agents used in food and medication to treat certain conditions. This study evaluated the impact of concomitant consumption of CA and PA on ERL and GEF pharmacokinetic parameters (PKs). The PKs of ERL and GEF were investigated in rats after four weeks of CA and PPA consumption in low (175 mg/kg) and high (100 mg/kg) doses using UPLC-MS/MS. Data indicated that acidifying agents altered PKs of ERL and GEF dose-dependently. High doses of CA and PPA significantly increased the Cmax of ERL by 103% and 218%, the AUC_0-72 by 35% and 78%, respectively, while reducing CL/F by 44% with CA and 74% with PPA. For GEF, Low and high doses of PPA increased C_max and T_max with a reduction of CL/F. A low dose of CA did not impact C_max, significantly decreased AUC_0-72 (28%), and increased CL/F (16%). The high dose of CA increased C_max (13%) with no impact on AUC_0-72 and decreased CL/F (23%). Furthermore, both doses of acidifying agents significantly increased liver enzyme levels and reduced body weight within two weeks. The results demonstrated that the PKs of both drugs were changed, and caution and close monitoring should be taken with ERL and GEF when co-administered with an acidifying agent.

Durvalumab is an immune checkpoint inhibitor that targets PD-L1 and is used for malignancies such as hepatocellular carcinoma. Although effective, it may cause immune-related adverse events, including rare cases of myocarditis (0.06% to 1%), which usually appear early. This complication results from immune response-induced damage to the myocardium, highlighting the importance of prompt detection and management to prevent potentially fatal outcomes. This report describes a 70-year-old woman with advanced hepatocellular carcinoma who developed myocarditis after receiving a single dose of durvalumab. The patient presented with atypical chest pain, shortness of breath, and gastrointestinal symptoms. Initial investigations revealed elevated cardiac biomarkers, including Troponin I and CK-MB, and an ECG showing sinus tachycardia and right bundle branch block. A cardiac MRI confirmed non-ischemic myocardial injury, leading to a diagnosis of ICI-induced myocarditis. The patient was treated with high-dose corticosteroids, resulting in rapid clinical improvement and stabilization of cardiac function. A multidisciplinary approach involving cardiology, oncology, and clinical pharmacy was crucial in managing this complex case. This case highlights the importance of heightened vigilance among healthcare providers when administering ICIs, particularly durvalumab, due to the risk of myocarditis. Early detection and prompt intervention are essential to manage ICI-related adverse events and prevent severe outcomes. The successful treatment of this patient demonstrates the importance of a multidisciplinary approach in tackling the complexities of ICI-induced myocarditis. Further research is necessary to optimize management strategies and follow-up protocols for patients experiencing this rare but serious adverse event.

This study aimed to establish a method for quantifying baicalin (BC) in rabbit ocular tissues and plasma, and evaluate the pharmacological efficacy and pharmacokinetic properties of BC and BC@HS15/DSPE-PEG2000-L-Val, a novel ocular formulation for dry eye treatment. BC@HS15/DSPE-PEG2000-L-Val or free BC was administered via eye drops to benzalkonium chloride (BAC)-induced dry eye mice. Corneal and conjunctival tissues were assessed for anti-dry eye efficacy. BC concentrations in cornea, conjunctiva, aqueous humor, and ocular plasma were quantified using LC-MS/MS. Noncompartmental pharmacokinetic parameters (AUC, Tmax) were calculated using DAS 2.0 software. The method demonstrated excellent linearity (0.50-500.00 ng/mL, r > 0.9905), precision (RSD < 10%), and accuracy (± 13%). Compared to free BC, BC@HS15/DSPE-PEG2000-L-Val significantly increased tear secretion, reduced MMP-3/MMP-9 expression, and preserved corneal epithelium integrity. In the micelle group, corneal and conjunctival Cmax values were 2.7- and 3.6-fold higher than the solution group, respectively. A sensitive and validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to measure baicalin concentrations in ocular plasma and tissues of rabbits. BC@HS15/DSPE-PEG2000-L-Val for treating dry eye demonstrated significantly superior outcomes. The nano-micelle notably enhanced BC concentration on the ocular surface and effectively prolonged its retention time.

In Saudi Arabia, the regulation of community pharmacies currently falls under the Ministry of Health (MOH). There is a need to shift the regulatory framework of community pharmacies to be under the Saudi Food and Drug Authority (SFDA) to align with global standards. However, there is limited knowledge about the perceptions of pharmacists regarding the current regulatory framework in community pharmacies in the Kingdom of Saudi Arabia (KSA).

Objectives: This study aims to assess pharmacists' knowledge, perceptions, and preferences regarding the current regulatory framework of community pharmacies and feasibility of transitioning regulatory oversight to SFDA.

Methodology: A cross-sectional survey design was used to assess the regulation of community pharmacies in Saudi Arabia. The sample consisted of 139 pharmacists from various sectors, selected through random sampling. A structured questionnaire focusing on regulation, awareness, and perceptions was distributed online. The questionnaire's validity and reliability were ensured through expert review. Descriptive statistics in SPSS were used for data analysis.

Results: The survey findings revealed a diverse representation across the pharmaceutical sector. Hospital pharmacists formed the largest group (37.4%, n = 52), followed by regulatory field workers from the Ministry of Health (21.6%, n = 30) and SFDA (20.1%, n = 28), pharmaceutical industry professionals (11.5%, n = 16), and community pharmacists (9.4%, n = 13). Most participants (51.8%, n = 72) had 1-5 years of experience, while 31.7% (n = 44) had 6-10 years, and 16.5% (n = 23) had more than 10 years of experience. Regarding current regulatory oversight, the majority (82.7%, n = 115) reported being under MOH regulation, with 12.2% (n = 17) under SFDA oversight. The study revealed high awareness of current regulations (77.0%, n = 107), though most participants (62.6%, n = 87) expressed dissatisfaction with the current regulatory framework. Notably, 77.0% (n = 107) preferred SFDA as the future regulator, and 80.6% (n = 112) believed SFDA would perform better in regulating the sector. Most participants demonstrated strong agreement with proposed regulatory changes, with 78.4% (n = 109) agreeing to P1 and 79.1% (n = 110) to P4 statements regarding regulatory reform.

Conclusion: The study reveals strong sector-wide preference among pharmaceutical professionals for transitioning community pharmacy regulation to SFDA, driven by dissatisfaction with current MOH oversight. This consensus across all professional categories and experience levels indicates practitioners' expectations that SFDA regulation would enhance pharmaceutical service quality and regulatory effectiveness in Saudi Arabia.

Malaria remains a significant public health challenge in regions where it is endemic. Pregnant women and young children are particularly vulnerable to the disease. Effective and timely diagnostic methods are crucial for reducing severe health outcomes. These methods help prevent deaths and lessen the widespread clinical and epidemiological burden on at-risk populations. However, traditional methods involved in the process of malaria parasite detections such as microscopic examination of blood smear by medical trained technicians is known to be time consuming, purely subjective and highly prone to errors. Therefore, Artificial Intelligence (AI) based OD (Object Detection) model like YOLO are preferred for overcoming these issues faced by traditional approaches as YOLO is known to be more rapid and precise by predicting bounding boxes and class probabilities than other models. However, existing YOLO model face challenges such as higher localization error, struggle with small objects and better accuracy of the model. Therefore, proposed research work focuses on employing YOLOv3 model with modified MobileNetv2 in backbone structure for classifying Plasmodium vivax (P. vivax) cells with the aim of improving the performance and speed of the model for detecting objects as MobileNetv2 is known for its faster processing and reduced resource consumption. However, accuracy is still measured as one of the key downsides for detecting and classifying the classes of thin blood smear, therefore modified MobileNetv2 is used, where proposed TCL (Transformed Convolution Layer) is employed at bottleneck layer, where weights are calculated based on different classes of image features thereby making the process more effective for classifying the infected and uninfected malaria cells of thin blood smear images effective. Besides, the performance of the proposed model is evaluated by implementing different metrics where the findings obtained are accuracy value of 1.00, precision value of 0.98, recall of 0.98, F1 score of 0.97 and mean average precision (mAP) value of 0.90. The major contribution of the study focuses on providing a better diagnostic approach for medical professionals in order to obtain improved results.

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.

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.

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.

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.

Background: 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).

Objectives: To investigate specific CYP3A4 and CYP3A5 polymorphisms in SKTP and evaluate their influence on Tac dose requirements and trough levels.

Methods: 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.

Results: 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.

Conclusion: 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.