Journal of Pharmacology and Pharmacotherapeutics

MRSA and PRSP resistance has surged over 30 years, threatening clinical outcomes; China-developed cefathiamidine sodium, with enhanced pharmacokinetics, offers potent activity against these Gram-positive pathogens.

This study evaluates the pharmacokinetic profile of injectable ceftriamidine sodium in healthy volunteers and compares its pharmacokinetics with those of cefathiamidine.

This clinical trial was a randomized and controlled study. The ceftriamidine sodium group (administered ceftriamidine sodium or placebo) employed a double-blind design with multiple administrations and dose escalation, whereas the cefathiamidine group (administered cefathiamidine) utilized an open-label design with single and multiple continuous administrations. The clinical trial involved ceftriamidine sodium at doses of 3.0 and 4.0 g, corresponding to cefathiamidine doses of 0.5 and 2.0 g. Volunteers received the corresponding drug infusions as per the protocol, and a series of blood samples were collected at specified time points for pharmacokinetic analysis.

In the 3.0 and 4.0 g dose groups of ceftriamidine sodium, the t_1/2, T_max, and C_max were 1.98–2.11 h, 0.50 h, and 321.14–448.80 µg/mL, respectively. Upon reaching steady state after multiple doses of 3.0–4.0 g, no significant drug accumulation was observed. Following multiple administrations of cefathiamidine at 0.5 and 2.0 g, the peak time at steady state was 0.50 h, t_1/2 was 1.26–1.17 h, and C_max was 48.11–194.40 µg/mL.

The half-life of ceftriamidine sodium (1.98–2.11 h) is almost twice as long as that of cefathiamidine (1.17–1.26 h), indicating its pharmacokinetic superiority in reducing the frequency of administration.

Osteoarthritis (OA) is the most common form of arthritis affecting the elderly and obese population, and requires long-term medical management. Inflammatory pathways, possibly initiated by tissue damage and stress are involved in the pathogenesis of OA. Citrus medica Linn., known for its anti-inflammatory and analgesic properties, has been the focus of management of OA in recent years.

To explore the therapeutic potential of Citrus medica gel in Wistar Albino rat OA model with standard Aceclofenac gel.

An experimental interventional animal study was conducted in which OA was induced in 24 male Wistar Albino rats (12-week-old) using monosodium iodoacetate. The animals were observed for 1 week for signs of joint inflammation. They were then divided into four groups. Group A (standard) received Aceclofenac gel twice daily (BD) for 4 weeks. Group B received C. medica gel (0.2 g, 0.33% w/w) once daily (OD). Group C received C. medica gel (0.2 g, 0.33% w/w) BD, and Group D was kept as a disease control throughout the study. The results were compared between groups using one-way analysis of variance (ANOVA).

The double-dose C. medica gel regimen displayed a significant and earlier reduction in ankle joint circumference (ANOVA, p value < .001). Pain relief was observed, as evidenced by a favorable reversal of the arthritic index and score compared to the standard treatment.

This study highlights the potential of C. medica gel in reducing inflammation and pain associated with OA. These findings warrant further investigation through clinical trials.

Chronic diseases present a significant health risk, and global medication adherence for these conditions remains insufficient. Understanding the factors that affect adherence is essential.

This study aims to better understand medication adherence and the factors influencing non-adherence in Saudi Arabia.

A questionnaire-based survey was carried out among patients with chronic diseases in the Makkah region of Saudi Arabia from May 1 to August 31, 2024. Participants included individuals aged 18 and older using either prescribed or over-the-counter (OTC) medications. Descriptive statistics were employed to outline the participants’ characteristics, with categorical variables presented as frequencies and percentages. A chi-square test was utilized to examine the relationships between variables.

In total, 292 participants were included in this study. Their ages ranged from 18 to more than 50 years, with a mean age of 38.4 ± 12.5 years old and most of them (72.6%) were female. For chronic diseases, the most reported were hypertension (HTN) (28.8%), diabetes (22.6%), and dyslipidemia (22.3%). The majority of patients (77.7%) were taking 1–3 medications daily, 13.5% were taking 4–6 drugs, and 3.8% were taking 7–9 medications. Medication adherence was significantly associated with informed medical instruction (p < .01), family and friend support (p < .01), and the number of drugs received daily (p < .004).

Focusing on factors such as clear medical instructions, social support, and the number of medications prescribed could boost medication adherence and lead to better health outcomes for patients with chronic diseases in Saudi Arabia.

Alzheimer’s disease (AD) is a long-term neurodegenerative condition that leads to the gradual deterioration of nerve cells. The goal of this study is to use computational drug discovery (CDD) techniques to discover lead compounds that target Amyloid-beta A4 (AβA4) as a potential target for AD.

Quantitative structure-activity relationship (QSAR) modeling is used in this study to compare different machine learning (ML) models aimed at predicting the potency negative logarithm of IC₅₀ (pIC₅₀) of candidate compounds, which are then validated by molecular docking based on their binding affinity. A non-redundant dataset consisting of 1,241 compounds for AβA4 was retrieved from the ChEMBL database. 880 substructure fingerprints were used to define these compounds, followed by building 42 ML models and comparison. The Kennard–Stone algorithm was employed to select a diverse set of 30 compounds from the set of active inhibitors for testing. The application programming interface (API), named NeuroIC₅₀, was developed and deployed.

The histogram-based gradient boosting regression (HGBR) tree has achieved the optimal performance compared to other regression models, as determined by its root mean square error (RMSE) of 0.73, R² value of 0.65, and time efficiency of 0.78. Random forest regression (RFR)-HGBR-derived Gini index revealed the importance of features, include SubFP23, SubFP405, and SubFP577 in the compounds.

The lead compound (CHEMBL5080033) with a pIC₅₀ of 8.67 M and a binding energy of −7.6 kcal/mol was identified. This ML-based QSAR modeling and docking approach is an effective strategy for accelerating drug discovery.

Doxorubicin (DOX), an anthracycline-based chemotherapeutic agent, has been widely used as a first-line treatment for several cancers, including hematological and solid tumors, but its clinical utility is limited by severe cardiotoxicity and nephrotoxicity.

This study aims to evaluate the protective effects of pumpkin oil (PO), olive oil (OO), and their combinations against DOX-induced nephrotoxicity in rats.

A total of six groups of rats were established for this experiment. The first group of rats served as a normal control and received only the vehicle for 10 days. The second group served as a positive control and received only the same pumpkin-to-OO ratio (1:1 v/v) orally daily for 10 days. The third group was a toxic group and received DOX 20 mg/kg intraperitoneally only on the fourth day. Groups four, five, and six were treated orally with pumpkin, olive, or a combination of both oils (10 mL/kg) daily for 10 days, followed by a single intraperitoneal dose of 20 mg/kg DOX on the 7th day.

The toxic group exhibited a significant increase in oxidative stress thiobarbituric acid reactive substances (TBARS), pro-inflammatory cytokines (interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα)), apoptotic markers (caspase-3 and caspase-9), renal markers (triglyceride (TG), blood urea nitrogen (BUN), uric acid (UA), and creatinine (Cr)), and deoxyribonucleic acid (DNA) fragmentation while antioxidant (glutathione (GSH)) and antioxidant enzymes (glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), and superoxide dismutase (SOD)) were significantly reduced in comparison to the normal control. These alterations were notably reversed upon treatment with pumpkin and OO alone, as well as a combination, in comparison to the toxic group. These changes were also reflected in the histopathology of the kidney. No significant difference was observed between the positive and normal controls.

Thus, we can conclude that the potential synergistic effects of pumpkin and OO in mitigating oxidative stress and inflammatory cytokines, which may play a significant role as a native medicine in the future, with limitations.

Down syndrome (DS), caused by trisomy 21, is characterized by chronic oxidative stress resulting from overexpression of the superoxide dismutase 1 (SOD1) gene without a proportional increase in downstream antioxidant enzymes such as glutathione peroxidase (GPx). This imbalance leads to hydrogen peroxide accumulation, contributing to neurodegeneration and systemic complications. Plant-derived phytochemicals with antioxidant properties may offer a multi-target strategy to restore redox homeostasis in DS.

The present study aimed to evaluate phytochemicals derived from Platanus orientalis for their potential to modulate oxidative stress in Down syndrome by targeting the SOD1–GPx redox axis using in-silico molecular docking and pharmacokinetic analysis.

Seven phytochemicals were selected from the IMPPAT database based on reported antioxidant activity. The three-dimensional structures of SOD1 (PDB ID: 2C9V) and GPx (PDB ID: 2R37) were retrieved from the Protein Data Bank and prepared for docking. Molecular docking was performed to assess binding affinities and interaction profiles. Drug-likeness, pharmacokinetic parameters, and blood–brain barrier permeability were evaluated using in-silico ADMET prediction tools.

All selected phytochemicals exhibited favorable binding interactions with both SOD1 and GPx, with binding energies ranging from −5.0 to −7.5 kcal/mol for SOD1 and −4.8 to −6.7 kcal/mol for GPx. Tiliroside demonstrated the strongest affinity towards SOD1, while kaempferol and betulinic acid showed stable and consistent interactions with both targets. Five compounds—platanin, kaempferol, caffeic acid, allantoin, and betulinic acid—displayed acceptable drug-likeness profiles, although none were predicted to cross the blood–brain barrier.

Platanus orientalis–derived phytochemicals demonstrate promising dual-target interactions with SOD1 and GPx, supporting their potential role in modulating oxidative stress in Down syndrome. These findings warrant further experimental validation to explore their therapeutic relevance and translational potential.

Buprofezin, a thiadiazine insecticide globally recognized as a molting inhibitor, is widely used for controlling whitefly and other insect pests.

This study investigated the impacts of sub-lethal buprofezin concentrations (0.15, 0.30, and 0.60 mg/L) on adult Clarias gariepinus fish over an 8-day exposure period.

The 96-h LC₅₀ was determined to be 2.4 mg/L. During the sub-lethal treatment, genotoxic analysis, hematological examination, biochemical analysis, and histopathological observations were performed.

Genotoxic analysis revealed a gradual, concentration-dependent increase in micronucleus abnormalities, including binucleus, blebbed nuclei, lobed nuclei, and notched nuclei. Hematological examination revealed a considerable increase in white blood cells, neutrophils, monocytes, eosinophils, basophils, and mean corpuscular hemoglobin, alongside a reduction in lymphocytes, mean corpuscular hemoglobin concentration, red blood cell distribution width, and platelets. Biochemical analysis indicated a decline in alkaline phosphatase and total protein levels, while aspartate aminotransferase, alanine aminotransferase, and total glucose levels progressively increased with higher buprofezin doses. Histopathological observations revealed significant alterations in gills, such as cellular proliferation leading to lamellae fusion. The liver exhibited necrosis, vacuolization, hemorrhage, sac formation, enlargement, and rupturing of hepatocytes.

These findings collectively demonstrate that buprofezin induces significant genotoxic, hematological, biochemical, and tissue abnormalities in C. gariepinus, highlighting its potential ecotoxicological risks in freshwater ecosystems.

Repurposing of a hydroxylmethylglutaryl coenzyme A reductase inhibitor like simvastatin has gained significant interest in oncologic treatment owing to the pleiotropic effects. However, the role of simvastatin in inhibiting epithelial-mesenchymal transition (EMT), a critical process in cancer metastasis, remains underexplored.

To investigate the anti-EMT potential of simvastatin in human breast cancer MCF-7 cells.

MCF-7 cells were treated with simvastatin, and the anti-proliferative and pro-apoptotic effect were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and fluorescence double staining method, respectively. Cell migration and cell aggregation assays were carried out to determine EMT-associated activities. A key regulator of EMT, β-catenin activity was measured using an indirect enzyme-linked immunosorbent assay, and the gene expression in response to simvastatin treatment was analyzed by reverse transcriptase polymerase chain reaction.

A dose-dependent cytotoxic activity was induced by simvastatin in MCF-7 cells, associated with morphological alterations indicative of apoptosis. Enhanced apoptotic cell death on simvastatin administration was validated by fluorescence nuclear staining. A marked reduction in migratory capacity and cell aggregation was observed in simvastatin-treated cells. Activity of β-catenin and the messenger ribonucleic acid expression were found to be downregulated.

Simvastatin effectively suppressed EMT-related processes in MCF-7 breast cancer cells by inhibiting cell proliferation, migration, aggregation, and β-catenin expression. These findings highlight the potential of simvastatin as a therapeutic agent for preventing breast cancer metastasis through EMT inhibition.

Patients with acute promyelocytic leukemia (APML) undergoing induction therapy are severely immunocompromised and prone to opportunistic infections. Tuberculosis (TB), though less commonly considered, can complicate the clinical course, particularly in endemic regions.

To emphasize the need to consider extrapulmonary TB in APML patients with persistent fever and non-resolving pleuro-pulmonary abnormalities.

An APML patient receiving arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) developed persistent high-grade fever. High-resolution computed tomography (HRCT) and microbiological evaluation were performed. TB DNA was detected from mediastinal lymph nodes. Due to hepatic and renal dysfunction, a modified anti-tubercular treatment (ATT) regimen was initiated. Serial HRCT scans from February 17 to February 25, 2025 were used for follow-up.

Initial HRCT revealed right pleural effusion, adjacent lung collapse, bilateral centrilobular nodules, and mediastinal lymphadenopathy. Follow-up imaging showed marked reduction in pleural effusion with persistent pleural thickening and minimal residual air near the drain site, suggesting an ongoing infectious process. The patient demonstrated clinical improvement with continued modified ATT and APML-directed therapy.

Persistent pleural thickening despite decreasing effusion in immunocompromised APML patients should raise suspicion of tuberculosis. Early microbiological confirmation, serial imaging, and multidisciplinary management are crucial for timely diagnosis and favorable outcomes, particularly in TB-endemic settings.

Regional anaesthesia is widely preferred for upper limb surgeries, particularly those performed below the elbow; however, the limited duration of action of local anaesthetics remains a clinical challenge. The addition of adjuvants such as magnesium sulphate (MgSO4) contributes to better block characteristics and sustained analgesic effect. Purpose: This study was designed to investigate whether varying doses of perineural MgSO4 influence the characteristics of ultrasound-guided infraclavicular brachial plexus block performed with bupivacaine.

Following approval from the Institutional Ethics Committee and registration with the Clinical Trials Registry-India, this prospective randomised double-blind single-centre study was undertaken in 90 ASA I-II adults undergoing elective upper limb surgery. Participants were randomly allocated into three groups (n = 30 each). All groups received 20 mL of 0.5% bupivacaine, with Group A receiving 125 mg MgSO4, Group B 250 mg MgSO4 and Group C 500 mg MgSO4, diluted with normal saline to maintain equal volume. The principal outcome measure was postoperative analgesia duration, with block characteristics and adverse events analysed as secondary outcomes. Continuous variables were analysed using one-way analysis of variance, and categorical variables using the Chi-square test.

The duration of analgesia increased significantly in a dose-dependent manner, with Group C demonstrating the longest duration (711 ± 38.98 min), followed by Group B (582.17 ± 29.64 min) and Group A (466.33 ± 32 min) (p < .001). Sensory and motor blockade developed more rapidly and persisted longer in Group C than in the other two groups. None of the participants experienced block failure or adverse effects such as hypotension, bradycardia, nausea or vomiting.

Perineural MgSO4 significantly enhances the duration of analgesia and improves block characteristics in ultrasound-guided infraclavicular brachial plexus block in a dose-dependent manner. Among the doses studied, 500 mg MgSO4 provided the most prolonged analgesia without increasing adverse effects, supporting its safe and effective use as an adjuvant to bupivacaine in upper limb surgeries.

Nigella sativa is the source of thymoquinone (TQ), an active phenolic compound with numerous pharmacological properties, including anti-tumor, anti-angiogenic, and antioxidant activities. Nevertheless, the mechanism by which TQ exerts its therapeutic effects and its potential utility in cancer treatment remain largely unknown.

This study examine the potential anticancer properties of TQ at a concentrations of 8, 12, and 16 µg in colon cancer cells (HCT116).

We investigated the effects of TQ in promoting apoptosis and inhibiting cell proliferation in colon cancer cells (HCT116) in the present study. It showed that in TQ-treated HCT116 cells, antioxidant levels (superoxide dismutase, catalase and glutathione) were reduced in a dose-dependent manner (8, 12, and 16 µg), and that TQ significantly increased the production of reactive oxygen species, lipid peroxidation in terms of malondialdehyde, and loss of cell viability.

Additionally, morphological changes and DNA fragmentation confirm that TQ induces oxidative stress-mediated apoptosis. Additionally, TQ treatment effectively increases the expression of Bax, caspase-9, and caspase-3 while decreasing the expression of Bcl-2 and Bcl-xl in colon cancer cells.

Our findings collectively demonstrate that TQ’s anti-tumor effects in HCT116 colon cancer cells reduce cell proliferation and promote apoptosis by modifying pro- and anti-apoptotic molecular events. Our results suggest that TQ could be utilized as a therapeutic agent to treat colon cancer.

Machine Learning-powered Internet of Medical Things (MLIoMT) is a burgeoning framework poised to transform healthcare, particularly in the timely identification of heart disease.

This article proposes an innovative MLIoMT structure aimed at leveraging machine learning (ML) algorithms for heart disease detection.

Through the integration of wearable sensors, mobile applications, cloud computing, and advanced ML techniques, MLIoMT enables continuous monitoring of vital signs and cardiac health indicators in real time. By analyzing this data stream, abnormalities indicative of heart disease can be detected early, facilitating timely intervention and personalized healthcare recommendations. The MLIoMT framework employs diverse ML methods such as deep learning and ensemble techniques to enhance the accuracy and reliability of heart disease prediction models.

The proposed structure holds promise for revolutionizing preventive healthcare, enabling proactive management of cardiac health and ultimately reducing the burden of heart disease. Results in terms of accuracy, precision, recall and F1 score show that the proposed system has better performance and efficiency.

Overall, MLIoMT represents a significant advancement in healthcare technology, with the potential to improve patient outcomes and enhance overall quality of life.

Epilepsy affects around 70 million people worldwide, with a higher prevalence in developing countries like Malaysia. Antiepileptic drugs (AEDs) such as carbamazepine, phenobarbitone, valproic acid, and phenytoin are essential for managing epilepsy, but their pharmacokinetic variability requires precise monitoring. Limited local data underscore the need to optimize therapeutic drug monitoring (TDM) practices in Malaysia to improve therapeutic outcomes.

This study evaluates the associations between TDM indications (breakthrough seizure, dosing adequacy, compliance, and suspected toxicity) and plasma concentrations of four commonly used AEDs to guide drug therapy in epilepsy management.

A retrospective, case-control study was conducted over 1 year in a tertiary care hospital, including patients on AEDs requiring TDM. Plasma drug levels were analyzed in relation to breakthrough seizures, dosing adequacy, compliance, and suspected toxicity. Statistical analysis was performed using SPSS, focusing on descriptive statistics and odds ratios with 95% confidence intervals.

A total of 780 samples were analyzed, revealing significant variations in plasma concentrations of AEDs relative to TDM indications. Carbamazepine had the highest proportion within the therapeutic range (78.9%), followed by phenobarbitone (61.3%). Valproic acid and phenytoin had lower therapeutic range proportions (40.6% and 18.1%, respectively). Non-compliance with carbamazepine impacted outcomes, while phenytoin and valproic acid were strongly linked to toxicity.

The study emphasizes the importance of TDM in epilepsy management, particularly for optimizing dosages and monitoring compliance and toxicity. It suggests that Malaysian TDM guidelines should focus on more frequent monitoring of AEDs like phenytoin and valproic acid, which show higher rates of sub-therapeutic and toxic levels. These insights could improve AED therapy and patient care in Malaysia.

Immunotherapy has wholly changed how cancer is treated by using the body’s immune system to eliminate cancer cells. Cancer vaccines, chimeric antigen receptor T-cell (CAR-T) treatments, and immune checkpoint inhibitors (ICIs) are at the forefront, each with a unique method for boosting anti-tumor immunity. Despite its success, there are still issues with resistance mechanisms, limited effectiveness in some types of cancer, and optimizing combination treatments.

The goal of this study is to give a comprehensive summary of the pharmacological approaches to cancer immunotherapy, such as cancer vaccines, CAR-T cell treatments, and ICIs. It overviews these treatments’ mechanics, clinical activity, ongoing clinical studies, difficulties, and potential prospects.

A thorough search of the available literature and clinical trial data was used to perform the narrative review. The study incorporated publications from several sources, including PubMed and clinical trial registries, to provide a current picture of the state of cancer immunotherapy. Critical therapeutic approaches were examined in light of new therapy paradigms, clinical findings, and molecular causes.

ICIs, such as cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors, have shown promise, particularly in treating non-small-cell lung cancer (NSCLC) and melanoma. Trials are being conducted to assess the use of CAR-T cell therapy in solid tumors after it demonstrated efficacy in hematologic malignancies. The future is being transformed by cancer vaccinations, both preventative (like the human papillomavirus (HPV) vaccine) and therapeutic, with combination therapy showing promise in overcoming resistance and enhancing effectiveness.

ICIs, CAR-T cells, and cancer vaccines are driving the revolution in cancer immunotherapy. Even though the treatments offer much promise, additional research is needed to overcome the limitations of the present day, increase response rates, and expand their uses. Clinical trials and innovation will determine the future of cancer treatment.

Autoimmune and inflammatory diseases, such as rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and psoriasis, are typified by immune dysregulation resulting in chronic inflammation and progressive tissue injury. Standard treatments, including corticosteroids, non-steroidal anti-inflammatory drugs, and disease-modifying anti-rheumatic drugs, are often of limited efficacy, have significant side effects, and are challenged by drug resistance.

This narrative review discusses new pharmacotherapeutic approaches to autoimmune and inflammatory diseases with a focus on biologic drugs, small-molecule inhibitors, gene therapy, and nanotechnology drug delivery systems.

A systematic literature search was performed using PubMed, Scopus, and Web of Science, covering clinical trials, pharmacological advances, and expert reviews of the past decade. The review highlights trends in immunotherapy, biomarker-stratified treatment selection, and new therapies for autoimmune diseases.

Biologic drugs, including tumor necrosis factor-alpha inhibitors, interleukin-17 inhibitors, and Janus kinase-signal transducer and activator of transcription inhibitors, have shown pertinent increases in disease remission rates and lowered systemic toxicity. However, constraints include high cost, resistance, and restricted access. Small-molecule inhibitors and precision immunotherapies enable patient-specific treatments with enhanced efficacy, but resistance and accessibility are significant hurdles. Breakthroughs in nanomedicine, clustered regularly interspaced short palindromic repeats-CRISPR associated protein 9 (CRISPR-Cas9) gene-editing, and artificial intelligence-assisted drug discovery hold much promise for overcoming these issues and providing more efficient and targeted treatments.

Precision pharmacotherapy has transformed autoimmune disease treatment by providing mechanism-based, patient-specific approaches. Future studies should aim to improve biomarker-guided therapies, enhance drug accessibility, and incorporate AI-based innovations to maximize clinical outcomes.