Pakistan journal of pharmaceutical sciences最新文献

{"title":"Low-dose dihydroartemisinin resensitizes lung cancer cells to cisplatin by suppressing interleukin-6 release by macrophages.","authors":"Jie Ruan, Jinbao Yin, Xuan Zeng, Fagang Liu, Zhiyong Wang","doi":"10.36721/PJPS.2026.39.6.178.1","DOIUrl":"10.36721/PJPS.2026.39.6.178.1","url":null,"abstract":"<p><strong>Background: </strong>The clinical application of dihydroartemisinin (DHA) is limited by its pharmacokinetic profile, making high in vitro concentrations clinically unattainable. Its effects at physiologically relevant low doses, especially in the complex tumor microenvironment (TME), are poorly understood.</p><p><strong>Objectives: </strong>This study investigated how clinically attainable low-dose DHA affects the efficacy of cisplatin in lung cancer in both monoculture and macrophage co-culture conditions, thereby uncovering a novel TME-dependent mechanism.</p><p><strong>Methods: </strong>Using human lung cancer cells and THP-1-derived macrophages, we conducted viability and invasion assays and measured IL-6 levels in both monoculture and co-culture systems. The effects of DHA on cisplatin sensitivity and invasion were evaluated, and rescue experiments using recombinant IL-6 and neutralizing antibodies were performed.</p><p><strong>Results: </strong>Low-dose DHA antagonized cisplatin cytotoxicity in monoculture but potently enhanced cisplatin-induced cell death after co-culturing with macrophages. Mechanistically, this sensitization was mediated via DHA-mediated inhibition of IL-6 secretion by macrophages. Adding exogenous IL-6 partly reversed this effect, while an IL-6 neutralizing antibody mimicked this effect. Furthermore, cisplatin paradoxically promoted cancer cell invasion by inducing IL-6 release from macrophages, which was efficiently blocked by low-dose DHA via the same pathway.</p><p><strong>Conclusion: </strong>At clinically relevant concentrations, the principal antitumor property of DHA lies in TME modulation rather than direct cytotoxicity. By inhibiting macrophage-derived IL-6, DHA simultaneously mitigated chemoresistance and invasion, resensitizing lung cancer cells to cisplatin. These findings provide a mechanistic rationale for combining DHA with platinum-based chemotherapy.</p>","PeriodicalId":19971,"journal":{"name":"Pakistan journal of pharmaceutical sciences","volume":"39 6","pages":"1873-1880"},"PeriodicalIF":0.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges to antibiotic stewardship: A cross-sectional study on self-reuse and disposal practices of leftover antibiotics.","authors":"Uroosa Kanwal, Syed Shaukat Ali Muttaqi Shah, Saba Razzak, Muhammad Ali, Ale Zehra, Sana Ejaz, Sana Bibi, Raahim Ali, Shoaib Nawaz, Sana Ali","doi":"10.36721/PJPS.2026.39.6.171.1","DOIUrl":"10.36721/PJPS.2026.39.6.171.1","url":null,"abstract":"<p><strong>Background: </strong>Antimicrobial resistance (AMR) is a growing global health threat, primarily driven by the inappropriate use of antibiotics and unsafe disposal practices. In developing countries like Pakistan, the misuse of leftover antibiotics through self-medication and improper disposal remains a poorly addressed public health concern.</p><p><strong>Objectives: </strong>This study aimed to describe the prevalence, patterns and associated factors of self-reuse and disposal practices of leftover antibiotics among residents of Karachi, Pakistan and to identify gaps affecting antibiotic stewardship.</p><p><strong>Methods: </strong>A descriptive, cross-sectional study was conducted using a validated online questionnaire targeting adults (≥18 years) residing in Karachi. A total of 385 responses were collected via non-probability sampling. The study was conducted from 10/02/2025 to 03/06/2025. Descriptive statistics and chi-square tests were applied using SPSS version 26 to evaluate associations between sociodemographic factors and antibiotic-related behaviours.</p><p><strong>Results: </strong>Approximately 24% of participants did not complete their prescribed antibiotic course, predominantly because of symptom resolution. Over half (56%) reported retaining leftover antibiotics and 43% admitted to reusing them without professional consultation, largely due to previous successful outcomes. A significant association was observed between educational level and perceptions of the safety of antibiotic reuse (p < 0.001). Disposal practices were suboptimal, with 70% discarding expired antibiotics in household trash and only 8% utilizing pharmacy take-back services. Counselling on proper disposal varied significantly by socioeconomic status (SES) (p = 0.009), with the highest rate reported among low SES participants (37.5%), but overall awareness of disposal programs remained low.</p><p><strong>Conclusion: </strong>The findings highlight concerning patterns in antibiotics storage, self-use and disposal practices in Karachi. These patterns suggest a need for public educational, pharmacist-led interventions and improved access to medication take-back programs to promote safer practices and reduce AMR risk.</p>","PeriodicalId":19971,"journal":{"name":"Pakistan journal of pharmaceutical sciences","volume":"39 6","pages":"1802-1816"},"PeriodicalIF":0.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics and factors affecting quality of life in children with congenital adrenal hyperplasia.","authors":"Shiyi Xu, Zhen Li, Qingxian Fu, Qiuting Lin, Hui Liu","doi":"10.36721/PJPS.2026.39.6.151.1","DOIUrl":"10.36721/PJPS.2026.39.6.151.1","url":null,"abstract":"<p><strong>Background: </strong>Congenital Adrenal Hyperplasia (CAH) is a group of disorders characterized by impaired adrenal steroid hormone synthesis, with a wide spectrum of clinical manifestations. The prognosis of CAH depends on factors, such as clinical phenotype, treatment and management.</p><p><strong>Objectives: </strong>To analyze the factors influencing the quality of life in children with CAH.</p><p><strong>Methods: </strong>This retrospective study included 30 CAH patients divided into good prognosis (n=13) and poor prognosis (n=17) groups. Clinical characteristics, genetic mutations, treatment compliance, medication regimens and complications were analyzed by t-tests and logistic regression.</p><p><strong>Results: </strong>The good prognosis group presented better compliance (92.31% vs. 47.06%, P=0.017) and hormonal control (84.62% vs. 35.29%, P=0.01). The prevalence of the salt-wasting (SW) type of CAH was higher in the poor prognosis group (70.59% vs. 23.08%, P=0.038), while the simple virilizing (SV) type was higher in the good prognosis group (53.85% vs. 17.65%). The poor prognosis group received a higher hydrocortisone dose (16±3mg/m2/day) compared to the good prognosis group (12±4mg/m2/day, P=0.025). Complications such as hypertension (P=0.017), hyperpigmentation (P=0.026) and urinary incontinence (P=0.017) were more prevalent in the poor prognosis group.</p><p><strong>Conclusion: </strong>In children with CAH, the quality of life is significantly affected by treatment compliance, hormonal control, and the presence of complications.</p>","PeriodicalId":19971,"journal":{"name":"Pakistan journal of pharmaceutical sciences","volume":"39 6","pages":"1602-1610"},"PeriodicalIF":0.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147618940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spectrophotometric evaluation of sun protection and antioxidant potential of Artemisia maritima L. and Sophora mollis Royle from Hunza, Gilgit-Baltistan.","authors":"Nain Tara, Muhammad Jahangir, Sundas Shahzadi","doi":"10.36721/PJPS.2026.39.6.166.1","DOIUrl":"10.36721/PJPS.2026.39.6.166.1","url":null,"abstract":"<p><strong>Background: </strong>Excessive ultraviolet (UV) radiation in mountainous regions increases the risk of skin disorders, highlighting the need for effective natural photoprotective agents.</p><p><strong>Objectives: </strong>This study aims to evaluate the sun protection factor (SPF) and antioxidant potential of two underexplored plants, Artemisia maritima and Sophora mollis, collected from high-altitude areas of Gilgit-Baltistan, to assess their suitability as natural photoprotective agents.</p><p><strong>Methods: </strong>UV-Vis spectroscopy was used to assess free radical scavenging activity (DPPH and ABTS assays), along with total phenolic content (TPC) and total flavonoid content (TFC).</p><p><strong>Results: </strong>A. maritima exhibited a higher SPF value (17.27 ± 0.31) compared to S. mollis (7.68 ± 0.18). Similarly, A. maritima showed greater TPC (345.93 ± 0.62 mg GAE/g) and TFC (239.30 ± 0.47 mg QE/g) than S. mollis (297.38 ± 0.34 mg GAE/g and 55.26 ± 0.75 mg QE/g, respectively). Antioxidant activity, measured by IC50 values, was strongest for Trolox (50.45 ± 0.97 µg/mL), followed by A. maritima (119.52 ± 2.23 µg/mL) and S. mollis (244.46 ± 8.06 µg/mL). In ABTS assays, A. maritima and S. mollis inhibited 68.3% and 60.2% of free radicals, respectively.</p><p><strong>Conclusion: </strong>These findings suggest that A. maritima possesses strong photoprotective and antioxidant properties, highlighting its potential as a promising natural sunscreen candidate, while S. mollis may provide moderate photoprotection suitable for complementary cosmetic or dermatological formulations.</p>","PeriodicalId":19971,"journal":{"name":"Pakistan journal of pharmaceutical sciences","volume":"39 6","pages":"1751-1758"},"PeriodicalIF":0.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147618995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Jin Ge Fang decoction mitigates alcoholic liver injury in rats via modulation of the TLR4/NF-κB signaling axis.","authors":"Shuifang Chen, Xuemei Chen, Liangong Peng, Yihui Huang, Yiqing Lin, Yinglian Cai, Qianwen Zheng","doi":"10.36721/PJPS.2026.39.6.157.1","DOIUrl":"10.36721/PJPS.2026.39.6.157.1","url":null,"abstract":"<p><strong>Background: </strong>Alcoholic liver disease (ALD) poses a significant global health challenge by causing progressive damage due to excessive alcohol consumption, highlighting the urgent need for effective treatments. Jin Ge Fang (JGF) is a traditional formulation whose potential hepatoprotective mechanism remains to be fully elucidated.</p><p><strong>Objectives: </strong>This study aimed to investigate the protective effects of JGF on ALD and explore its regulatory roles in oxidative stress, inflammatory cascades, and the Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway.</p><p><strong>Methods: </strong>An ethanol-induced ALD rat model was established and assessed histopathologically. Serum levels of hepatic function markers [aspartate transaminase (AST) and alanine transaminase (ALT)] and oxidative stress indicators [malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)] were measured. Inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β)] were quantified using enzyme-linked immunosorbent assay (ELISA). Protein expression related to the TLR4/NF-κB pathway was analyzed by Western blotting.</p><p><strong>Results: </strong>JGF treatment significantly improved liver histology, reducing steatosis and inflammatory infiltration. It markedly decreased serum AST and ALT activities, suppressed lipid peroxidation (as evidenced by reduced MDA levels), and enhanced endogenous antioxidant defenses (elevated SOD and GSH-Px activities). Furthermore, JGF significantly inhibited the release of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) and downregulated the protein expression of key mediators in the TLR4/NF-κB signaling pathway.</p><p><strong>Conclusion: </strong>JGF demonstrates significant hepatoprotective effects against ALD. Its benefits are likely mediated through a dual action of ameliorating oxidative damage and suppressing inflammatory activation, potentially via inhibition of the TLR4/NF-κB signaling cascade.</p>","PeriodicalId":19971,"journal":{"name":"Pakistan journal of pharmaceutical sciences","volume":"39 6","pages":"1655-1664"},"PeriodicalIF":0.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147619042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of oral piperaquine nanoparticles: A study on formulation, characterization and in-vivo performance.","authors":"Seema Bakht, Jahangir Khan, Maqsood Ur Rehman, Muhammad Asif Khan, Aziz- Ur-Rahman, Imran Tariq, Haya Hussain, Shujaat Ahmad, Rukhsana Ghaffar","doi":"10.36721/PJPS.2026.39.6.174.1","DOIUrl":"10.36721/PJPS.2026.39.6.174.1","url":null,"abstract":"<p><strong>Background: </strong>Piperaquine (PQ) is an anti-malarial bisquinoline BCS Class-II drug having low aqueous solubility and oral bioavailability, which affects its therapeutic effectiveness. Pharmaceutical Nanotechnology has proved its potential to overcome the challenges associated with poorly water-soluble drugs.</p><p><strong>Objectives: </strong>The fabrication of Piperaquine nanoparticles (PQ-NPs) through the antisolvent technique with subsequent characterization to improve the dissolution and bioavailability was the primary objective.</p><p><strong>Methods: </strong>PQ-NPs were prepared using anti-solvent precipitation Method. The polymers hydroxypropyl methylcellulose (HPMC) of 0.25%, polyvinylpyrrolidone (PVP-K30) of 0.25 %, and sodium lauryl sulfate (SLS) of 0.5 % were used as stabilizers. The Particle size, PDI, zetapotential, DSC, XRD, SEM, In-vitro dissolution, and in vivo study were performed for characterization of PQ-NPs.</p><p><strong>Results: </strong>The produced optimized PQ-NPs had a particle size of 184 nm, PDI of 0.248 and zeta potential of -31.4 mV. The NPs had a lower melting point and crystalline content, as shown by differential scanning calorimetry (DSC) and XRD. The SEM analysis confirmed the smaller particle size with a larger surface area. PQ-NPs showed a significantly faster release profile than raw drug, achieving 79.56% drug release in 5 minutes versus 27.31% (p < 0.05). Pharmacokinetic studies in mice revealed that C_max,T_max and AUC were significantly enhanced for PQ-NPs (C_max: 2.753 µg/ml vs. 1.233 µg/ml; T_max: 1.0 ± 0.3 hr vs 1.5 ± 0.3 hr, AUC: 1.119 µg.hr/ml vs. 0.954 µg.hr/ml.</p><p><strong>Conclusion: </strong>The findings indicate that PQ-NP were successfully fabricated, having substantial improvements in solubility, dissolution rate, and bioavailability, making them a promising approach for enhancing the therapeutic performance.</p>","PeriodicalId":19971,"journal":{"name":"Pakistan journal of pharmaceutical sciences","volume":"39 6","pages":"1834-1842"},"PeriodicalIF":0.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical assessment and early intervention for deviations in children's growth and development.","authors":"Guangqun Tang, Juan Wan, Jianying Liu, Maojia Zhu, Rui Liu","doi":"10.36721/PJPS.2026.39.6.173.1","DOIUrl":"10.36721/PJPS.2026.39.6.173.1","url":null,"abstract":"<p><strong>Background: </strong>Chinese adults' and children's heights have grown over two decades, but many parents remain unaware of the main factors affecting their children's height.</p><p><strong>Objectives: </strong>This study analyzed clinical and early pharmacological interventions for preventing and treating growth disorders and promoting normal growth in children with deviations.</p><p><strong>Methods: </strong>This study involves a non-randomized intervention. A retrospective study of 120 children examined at our hospital from March 2023 to February 2025 were divided into four groups based on height and development: short stature group (SS, n=28), less short stature group (LSS, n=32), early development group (ED, n=41) and central precocious puberty group (CPP, n=19). The SS group and LSS group received oral lysine, inositol, vitamin B12 solution + γ-aminobutyric acid (GABA) and the ED group and CPP group received oral Zhi Bai Di Huang Wan and all children were given health guidance. Clinically relevant information, such as baseline information, height growth values, and growth factor levels before and after treatment, was collected and compared among the four groups of children, and pre-treatment factors affecting children's height growth outcomes were also analyzed.</p><p><strong>Results: </strong>Before treatment, the four children's groups differed significantly (P < 0.05). After 3 and 6 months, all children's heights increased, with the fastest growth in the LSS group. Logistic regression showed sex and age before treatment were key factors affecting height. ROC curves revealed AUCs for sex, age and the model of 0.599(95% CI: 0.497-0.701), 0.774(95%CI: 0.686-0.861) and 0.818 (95% CI: 0.735-0.900).</p><p><strong>Conclusion: </strong>Clinical analysis and early intervention for children with growth deviations detected during school physical exams can restore normal growth, slow early bone age advancement, improve height outcomes and prevent or treat growth disorders.</p>","PeriodicalId":19971,"journal":{"name":"Pakistan journal of pharmaceutical sciences","volume":"39 6","pages":"1827-1833"},"PeriodicalIF":0.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polypharmacy and cognitive outcomes in elderly inpatients with Alzheimer's disease: A three-year retrospective study.","authors":"Youchao Hu, Jianping Jiang, Genming Shen, Xiaojie Ding","doi":"10.36721/PJPS.2026.39.6.170.1","DOIUrl":"10.36721/PJPS.2026.39.6.170.1","url":null,"abstract":"<p><strong>Background: </strong>Inpatient care for Alzheimer's disease (AD), often complicated by comorbidities, frequently involves polypharmacy (≥5 medications). The profile and cognitive consequences of sustained polypharmacy in these elderly inpatients require further investigation.</p><p><strong>Objectives: </strong>To investigate the status of polypharmacy in elderly inpatients with AD and its correlation with three-year cognitive outcomes, so as to provide a basis for clinical optimization of medication regimens.</p><p><strong>Methods: </strong>This study was a retrospective propensity score matching (PSM) cohort study. 300 AD inpatients who were hospitalized from March 2022 to March 2025 were included. Patients were stratified into polypharmacy and non-polypharmacy groups according to their polypharmacy status. The primary outcome was the incidence of cognitive decline (MMSE decline ≥3 points) at 3 years. Secondary outcomes were the association of CDR progression, rate of decline in MoCA, incidence of falls, all-cause rehospitalization, all-cause mortality and anticholinergic drug burden with cognitive outcomes.</p><p><strong>Results: </strong>After PSM, baseline characteristics were balanced (p>0.05). At the 3-year follow-up, the polypharmacy group had a significantly higher incidence of cognitive decline than the non-polypharmacy group (64.0% vs. 38.0%; RR=1.68, 95% CI: 1.33-2.13, p<0.001). Polypharmacy was also associated with faster CDR progression, a greater annual rate of MoCA decline and increased risks of falls (RR=1.82, p<0.01) and all-cause rehospitalization (RR=1.67, p<0.001). A high anticholinergic burden (ACB score ≥3) was identified as an independent predictor of cognitive decline (OR=2.5, 95%CI: 1.7-3.7, p<0.001).</p><p><strong>Conclusions: </strong>Our findings highlight polypharmacy as a key, modifiable risk for cognitive decline in AD, calling for structured medication management to mitigate this risk.</p>","PeriodicalId":19971,"journal":{"name":"Pakistan journal of pharmaceutical sciences","volume":"39 6","pages":"1792-1801"},"PeriodicalIF":0.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and evaluation of an antimicrobial stewardship-guided nursing care model for severe pneumonia: A retrospective cohort study.","authors":"Dongze Peng, Jing Fu, Simin Song","doi":"10.36721/PJPS.2026.39.6.164.1","DOIUrl":"10.36721/PJPS.2026.39.6.164.1","url":null,"abstract":"<p><strong>Background: </strong>Severe pneumonia is associated with high mortality and substantial antimicrobial exposure. Inappropriate antimicrobial use contributes to antimicrobial resistance and adverse drug reactions, potentially worsening outcomes.</p><p><strong>Objectives: </strong>To develop and evaluate an antimicrobial stewardship-guided nursing care model for patients with severe pneumonia.</p><p><strong>Methods: </strong>A single-center retrospective cohort study was conducted at the Second Medical Center of Chinese People's Liberation Army General Hospital (Beijing, China). Medical records of patients with severe pneumonia admitted between June 2024 and June 2025 were reviewed. Patients admitted in June-December 2024 received routine nursing care, whereas those admitted in January-June 2025 received a stewardship-guided nursing model. Outcomes were assessed until discharge or day 28, whichever occurred first.</p><p><strong>Results: </strong>Compared with routine care, the stewardship-guided cohort showed higher specimen collection compliance and antimicrobial selection rationality scores and lower drug utilization index (DUI), defined daily doses (DDDs) and inappropriate use of core antimicrobials (all p<0.05). Clinical cure rate was higher, length of stay and inflammatory-marker recovery time were shorter and complication rates were lower (all p<0.05). Nursing quality and patient satisfaction scores also improved (p<0.001).</p><p><strong>Conclusion: </strong>An antimicrobial stewardship-guided nursing care model was associated with improved antimicrobial-use quality, reduced antimicrobial-related complications and better clinical and nursing outcomes in patients with severe pneumonia; however, causal inference is limited by the non-concurrent retrospective design.</p>","PeriodicalId":19971,"journal":{"name":"Pakistan journal of pharmaceutical sciences","volume":"39 6","pages":"1735-1743"},"PeriodicalIF":0.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147618983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic and biotransformation analysis of thiophene- and dichlorophenyl-substituted indole-3-butyric acid hydrazones.","authors":"Sehar Madni, Aisha Rafique, Muhammad Usama Munir, Mahpara Gondal, Kanwal Rehman, Muhammad Sajid Hamid Akash","doi":"10.36721/PJPS.2026.39.6.161.1","DOIUrl":"10.36721/PJPS.2026.39.6.161.1","url":null,"abstract":"<p><strong>Background: </strong>The indole-3-butyric acid based hydrazones have gained attention due to their reported biological effectiveness; however, their in-vivo pharmacokinetic properties and metabolic pathways are yet inadequately investigated. Comprehending structure-dependent variations in absorption and metabolism is essential for the preliminary optimization of this scaffold.</p><p><strong>Objectives: </strong>The aim of the study was to comparatively assess the pharmacokinetics and biotransformation of two IBA-based hydrazones-4-indole-3-butane-(thiophen-2-ylmethylene) hydrazone (TIBH) and 1-(4-amino-3,5-dichlorophenyl) ethylidene-4-indole-3-butane hydrazone (DIBH) and to clarify the impact of structural substitution on their metabolic pathways in-vivo.</p><p><strong>Methods: </strong>UV-VIS spectrophotometry under verified linear circumstances assessed serum concentrations over 24 hr in healthy rats after a single oral dosage (10 mg/kg). Metabolites and temporal profiles were identified using LC-ESI-MS/MS. Biotransformer 3.0 was used for cheminformatic prediction of metabolic pathways and enzyme participation. In exploratory analysis, data are presented descriptively (mean ± SD).</p><p><strong>Results: </strong>TIBH demonstrated accelerated absorption with an earlier peak concentration (C_max at 4 hr) and a reduced half-life, while DIBH exhibited a delayed peak exposure (C_max at 8 hr) and extended systemic persistence. The LC-MS/MS study showed that both compounds went through a lot of Phase-I (hydrolysis, hydroxylation and deamination) and Phase-II (glucuronidation, sulfonation and acetylation) metabolism. This made them more polar and facilitating elimination. Different metabolite profiles showed how substitution changed metabolism. TIBH had faster oxidative and conjugative turnover, while DIBH was more stable with late stage dechlorination. The predicted routes and enzyme involvement aligned well with the experimental results.</p><p><strong>Conclusion: </strong>This research indicated that aromatic substitution significantly affects the pharmacokinetic and metabolic properties of IBA-based hydrazones. Despite its constraints due to an exploratory design and absence of pharmacological validation, the combined experimental and computational methodology offers mechanistic understanding of structure-metabolism connections and guides subsequent optimization and biological assessment of hydrazone scaffolds.</p>","PeriodicalId":19971,"journal":{"name":"Pakistan journal of pharmaceutical sciences","volume":"39 6","pages":"1699-1707"},"PeriodicalIF":0.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147619012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}