International journal of clinical pharmacology and therapeutics最新文献

{"title":"Alleviation of renal ischemia-reperfusion injury by quercetin, kaempferol, and luteolin in Shiwei Hezi pill (SHP): Network pharmacology and molecular docking analysis of a traditional Tibetan herbal agent","authors":"Drolma Gomchok, Hui Yang, Tana Wuren","doi":"10.5414/CP204701","DOIUrl":"10.5414/CP204701","url":null,"abstract":"<p><strong>Objective: </strong>The aim of the study was to utilize a systematic network pharmacology approach to explore the active components, targets, and pathways associated with the efficacy of Shiwei Hezi pill (SHP) in treating renal ischemia-reperfusion injury (RIRI).</p><p><strong>Materials and methods: </strong>We utilized online databases to identify common targets of SHP and RIRI. Functional annotation of genes using the Gene Ontology (GO) and enrichment analysis of pathways using the Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed using bioinformatics websites. Cytoscape was utilized to generate and visualize protein-protein interaction (PPI) networks. We employed specialist software to conduct molecular docking analysis on crucial constituents and targets in order to validate the interaction patterns between core ingredients and essential targets.</p><p><strong>Results: </strong>We screened 54 ingredients with good bioavailability in SHP and identified 204 shared targets between SHP and RIRI. Our data suggests that SHP may primarily target TNF, IL6, GAPDH, MMP9, PTGS2, and MMP6 in the therapeutic management of RIRI. The GO enrichment and KEGG pathway enrichment show that the mechanism of SHP treatment for RIRI involves multiple biological processes and signaling pathways. The molecular docking indicates that the three most potent active components of SHP (quercetin, kaempferol, and luteolin) have a strong likelihood of binding to TNF, IL6, GAPDH, MMP9, and PTGS2 with a high degree of affinity.</p><p><strong>Conclusion: </strong>This is the first exploration of the potential mechanism of Tibetan medicine formula SHP in treating RIRI using network pharmacology. Our research indicates that the various components of SHP could act on multiple targets and signaling pathways associated with RIRI. The findings in this study provide a theoretical basis and a novel method for the clinical therapy of RIRI.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541800","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":"Network pharmacology and experimental analysis of Yudantong decoction, a multi-immunomodulator for the treatment of intractable cholestatic liver disease: Identification of active agents, molecular targets, and mechanisms of action.","authors":"Xiaoming Wu, Linyi Hou, Jing Liu, Jing Hao, Chang Liu, Yan Hu, Qiang He","doi":"10.5414/CP204695","DOIUrl":"10.5414/CP204695","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Yudantong decoction (YDTD) is a therapeutic prescription for cholestatic liver disease (CLD) and is clinically effective in our medical institution. However, the exact constituents and mechanisms of YDTD in treating CLD remain unknown. This project aimed to explore the primary constituents and mechanism of YDTD in the treatment of CLD through ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS), network pharmacology, molecular docking technology, and in vivo experiments.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;The chemical constituents of YDTD were identified via UPLC-HRMS, and Bioinformatics analysis tool for molecular mechANism of traditional Chinese medicine (BATMAN-TCM) was employed to screen target proteins. Cytoscape 3.7.1 was used to build the herbal component-target network. The CLD targets were identified by querying the OMIM and DisGeNET databases and determining the overlap between the targets of the YDTD chemical constituents and those of CLD. The STRING database was utilized to construct a protein-protein interaction (PPI) network for subsequent analysis. Gene ontology (GO) biological process enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway enrichment analysis were carried out using the database for annotation, visualization and integrated discovery (DAVID) database. Molecular docking validation against core targets with PyMOL software was conducted for the active compounds. Finally, in vivo experiments were performed to investigate the therapeutic effect of YDTD in a murine model of α-naphthyl isothiocyanate (ANIT)-induced CLD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;YDTD has 112 major components, among which 59 have 1,478 potential targets. We identified a total of 1,957 potential therapeutic targets for CLD and 269 overlapping targets between CLD-associated targets and YDTD active component targets to construct a PPI network. Through topology analysis, IL-6, INS, IL1B, AKT1, BCL2, NFKB1, PTGS2, and TP53 were identified as key targets along with their corresponding primary chemical components. KEGG analysis revealed significant enrichment of the phosphoinositide 3-Kinase (PI3K)-Akt and nuclear factor Kappa-B (NF-κB) signaling pathways. The molecular docking results indicated strong binding affinities between glycyrrhizin-AKT1, l-arginine-IL1B, p-coumaric acid-IL1B, 2,4-dihydroxybenzoic acid-IL1B, p-coumaric acid-TNF, 2-hydroxycinnamic acid-TNF, uridine-AKT1, p-coumaric acid-IL6, and trigonelline-INS. In vivo experiments demonstrated that YDTD downregulated the expression of p-PI3K, p-AKT, p-NF-κB, IL-6, TNF-α, and IL-1β, and reduced immune cell infiltration in the liver to ameliorate liver damage in CLD patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The present study clarified the active components and potential anti-inflammatory mechanism of YDTD in treating CLD, providing a solid foundation for future research on its therapeutic m","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515332","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":"Differentiation of bone marrow mesenchymal stem cells modulated by Bushen Tian Sui decoction via the TGF-β1-Smad2/3 signaling pathway: In vitro evidence and potential clinical application in delayed fracture healing","authors":"Wei Xiong, Bingru Li, Jiamin Chen, Zichen Shao, Wei-Kang Sun, Song Li, Hualong Lu, Ling Cheng","doi":"10.5414/CP204746","DOIUrl":"10.5414/CP204746","url":null,"abstract":"<p><strong>Background: </strong>Bone-related disorders pose significant challenges in clinical practice. Bone marrow mesenchymal stem cells (BMSCs), as multipotent stem cells, play a pivotal role in bone regeneration. The TGF-β1-Smad2/3 signaling pathway is a well-recognized regulator of BMSC osteogenic differentiation. Traditional Chinese medicine (TCM), such as Bushen Tian Sui decoction (BSTSD), has shown potential in enhancing bone health; however, its molecular mechanisms remain poorly understood.</p><p><strong>Objective: </strong>Investigating the effects and underlying mechanisms of BSTSD on the osteogenic differentiation of BMSCs.</p><p><strong>Materials and methods: </strong>The impact of BSTSD on BMSCs was comprehensively analyzed using Cell Counting Kit-8 (CCK8), quantitative polymerase chain reaction (qPCR), western blot (WB), and immunofluorescence assays.</p><p><strong>Results: </strong>CCK8 results revealed the highest optical density (OD) values in the BSTSD + activator group at 24, 48, and 72 hours, indicating enhanced cell proliferation. qPCR analysis showed significantly increased expression levels of TGF-β1, Smad2, Smad3, SOX9, and RUNX2 in the BSTSD + activator group, suggesting a synergistic effect in promoting osteogenic and chondrogenic differentiation. WB results demonstrated elevated phosphorylation levels of Smad2 and Smad3 (p-Smad2, p-Smad3) in the BSTSD + activator group, while total Smad2 and Smad3 protein levels remained consistent among groups. Immunofluorescence assays confirmed the highest fluorescence intensity, positive area ratio, and cell count containing Smad2 and Smad3 proteins in the BSTSD + activator group, validating the synergistic effect of BSTSD and TGF-β1.</p><p><strong>Conclusion: </strong>BSTSD exhibits promising effects on BMSC differentiation and bone regeneration, mediated through the TGF-β1-Smad2/3 signaling pathway.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515624","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":"Pharmacokinetics and bioequivalence of ezetimibe tablet in healthy Chinese subjects under fasting and fed conditions.","authors":"Guan Liu, Hegui Yan, Baodong Yuan, Gang Li","doi":"10.5414/CP204642","DOIUrl":"10.5414/CP204642","url":null,"abstract":"<p><strong>Objective: </strong>The purpose of this study is to evaluate the pharmacokinetics (PK) parameters of an ezetimibe 10 mg (test drug) and assess its bioequivalence to the branded reference product in healthy Chinese subjects under fasting and fed conditions.</p><p><strong>Materials and methods: </strong>A single-center, randomized, open-label, four-period, two-sequence, full replicate crossover study was conducted in 88 healthy Chinese subjects under fasting or fed conditions. Subjects received a single oral dose of 10 mg ezetimibe tablet as test or reference formulation. There was a minimum 14-day washout period between each dose. Blood samples were collected at prescribed time intervals, the plasma concentration of free ezetimibe and total ezetimibe (ezetimibe + ezetimibe glucuronide) was determined by a validated ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Pharmacokinetik and bioavailability parameters were estimated via non-compartmental methods. Adverse events were also recorded.</p><p><strong>Results: </strong>40 and 48 eligible healthy subjects were enrolled in the fasted and fed study. Under fasting state, total ezetimibe with 90% confidence intervals (CIs) of C_max, AUC_0-t, and AUC_0-∞ were 87.17% (81.99 - 92.66%), 95.98% (92.38-99.72%), and 96.04% (91.37 - 100.95%), respectively. Under fed state, total ezetimibe with 90% confidence intervals (CIs) of C_max, AUC_0-t, and AUC_0-∞ were 98.71% (90.11 - 108.13%), 98.32% (94.71 - 102.06%), and 97.90% (92.68 - 103.42%), respectively. The 90% CIs of the ratio of geometric means (GMRs) of C_max, AUC_0-t, AUC_0-∞ of the test and reference formulation in both fasting and fed conditions fell within the conventional bioequivalence criteria of 0.80 - 1.25. No severe adverse events were observed.</p><p><strong>Conclusion: </strong>The test and reference 10-mg ezetimibe tablets were bioequivalent under fasting and fed conditions in Chinese subjects. Both preparations showed good safety and tolerability.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"38-46"},"PeriodicalIF":0.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545335","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":"Positive effects of magnesium supplementation in metabolic syndrome.","authors":"Sophia Kisters, Klaus Kisters, Tanja Werner, Jürgen Vormann, Faruk Tokmak, Timm Westhoff, Uwe Gröber, Hans-Georg Predel, Hannes Reuter","doi":"10.5414/CP204677","DOIUrl":"10.5414/CP204677","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Recent data show that magnesium supplementation decreases systolic and diastolic blood pressure values depending on the blood pressure levels and improves metabolic parameters in cardiovascular disease.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;In this context, we conducted a prospective, randomized, double-blind study on serum and ionized magnesium, systolic and diastolic blood pressure values, interleukin-6, vitamin D, and metabolic profile in 27 patients (13 male/14 female, age: 60.2 ± 12.5 years) with metabolic syndrome. All patients received 400 mg of oral magnesium supplementation daily. Parameters were measured before and after 6 and 12 weeks of treatment. 27 patients served as controls without additional magnesium treatment (10 male/17 female, age: 64.6 ± 13.2 years).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;There was no significant change in serum magnesium after 6 and 12 weeks of magnesium supplementation and in controls. Ionized magnesium significantly increased from 0.56 ± 0.05 to up to 0.63 ± 0.08 mmol/L (mean ± SD) (p &lt; 0.01). The ionized Ca&lt;sup&gt;++&lt;/sup&gt;/Mg&lt;sup&gt;++&lt;/sup&gt; ratio was significantly increased at baseline in about 32% of all patients; after 12 weeks of magnesium supplementation, the Ca&lt;sup&gt;++&lt;/sup&gt;/Mg&lt;sup&gt;++&lt;/sup&gt; ratio decreased significantly from 2.32 ± 0.22 to 2.04 ± 0.24 at the end of the study (mean ± SD, p &lt; 0.05). In the magnesium-treated group, there was a significant decrease in systolic and diastolic blood pressure values after 12 weeks (systolic: 134.6 ± 6.8 to 126.3 ± 5.6 mmHg, diastolic: 84.1 ± 3.9 to 79.4 ± 1.6 mmHg) (mean ± SD) (p &lt; 0.01). Additional magnesium supplementation decreased interleukin-6 values significantly from 4.94 ± 3.30 to 4.53 ± 6.89 pg/mL after 6 weeks to 3.01 ± 1.32 pg/mL after 12 weeks (mean ± SD) (p &lt; 0.01). In the control group, interleukin-6 was 3.73 ± 4.36 pg/mL before the start of the supplementation, 4.87 ± 4.35 pg/mL after 6 weeks, and 4.41 ± 3.15 pg/mL after 12 weeks (means ± SD) (n.s.). In patients receiving magnesium supplementation, vitamin D levels significantly improved from 17.93 ± 8.96 to 24.41 ± 10.20 ng/mL (mean ± SD) (p &lt; 0.05). HbA1c and serum cholesterol values improved under magnesium therapy, but the improvement did not reach significance. For statistical analysis, Mann-Whitney-U-Test was used.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Using supplementation with 400 mg magnesium for 12 weeks in patients with metabolic syndrome, ionized magnesium concentrations significantly increased, while serum magnesium did not change significantly. Both systolic and diastolic blood pressure values decreased significantly in the magnesium-treated group. Magnesium supplementation also significantly decreased interleukin-6 levels and increased vitamin D in patients. HbA1c and cholesterol levels improved with magnesium supplementation, but the improvement did not reach significance. The anti-inflammatory effects of magnesium as well as anti-arteriosclerotic eff","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"569-578"},"PeriodicalIF":0.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390398","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":"Identification of factors associated with vancomycin-induced acute kidney injury: A retrospective analysis using the Common Data Model.","authors":"Sang-In Park, Jung-Kyeom Kim, Uijeong Yu, Ji In Park","doi":"10.5414/CP204646","DOIUrl":"10.5414/CP204646","url":null,"abstract":"<p><strong>Objective: </strong>Previous findings on predictors of vancomycin-induced acute kidney injury (AKI) are inconsistent. We aimed to identify the predictors of vancomycin-induced AKI using the Observational Medical Outcome Partnership Common Data Model.</p><p><strong>Materials and methods: </strong>We analyzed data from patients treated with vancomycin between January 1, 2012, and May 31, 2022, who were positive for <i>Staphylococcus aureus</i> and had undergone oxacillin susceptibility tests. After excluding patients without data for vancomycin or baseline serum creatinine levels, 116 patients were included in the final dataset. Data up to the third measured vancomycin concentration were collected for each patient. Logistic regression models were used to estimate the odds ratio and 95% confidence interval for each variable associated with vancomycin-induced AKI.</p><p><strong>Results: </strong>High baseline serum creatinine levels, intensive care unit admission, and concurrent renal disorders were significantly associated with vancomycin-induced AKI. Although high trough levels or area under the curve values were not significantly associated with vancomycin-induced AKI, both were significantly higher in patients with AKI than in those without AKI at the second vancomycin concentration measurement. The proportion with trough levels > 20 mg/L was higher in patients with AKI than in those without AKI at the third measurement.</p><p><strong>Conclusion: </strong>Our findings revealed that underlying renal disease and intensive care unit admission are more significantly associated with vancomycin-induced AKI than vancomycin pharmacokinetic parameters or dosage, likely due to vancomycin concentration-based dosage adjustment in clinical settings. Our findings may help develop strategies for reducing the incidence of vancomycin-induced AKI; however, further prospective studies are essential.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"560-568"},"PeriodicalIF":0.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307733","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":"Evaluation of metronidazole oral monotherapy in anaerobic oral infections.","authors":"Najla Dar-Odeh, Ala'a Atef, Yara Flaifl, Dilnoza Bobamuratova, Basem Akily, Rayan Meer, Osama Abu-Hammad","doi":"10.5414/CP204565","DOIUrl":"10.5414/CP204565","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the indications and dosing regimens for oral metronidazole monotherapy (OMM) for the management of oral anaerobic infections (OAIs) other than periodontitis.</p><p><strong>Materials and methods: </strong>The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in literature of PubMed/Medline, Scopus, and Cochrane databases. Data were retrieved from reports published in English in the period January 1, 1980 - August 30, 2023. Joanna Briggs Institute Critical Appraisal Tools were used to assess study risk of bias.</p><p><strong>Results: </strong>A total of 228 articles were retrieved from the databases of which 16 met the inclusion criteria necessary for achieving the aims of the study. OAIs in which OMM was used or recommended included pericoronitis; necrotizing ulcerative gingivitis/periodontitis/stomatitis, osteomyelitis, acute periapical infection, and cellulitis. OMM was prescribed in dosages ranging from 200 to 500 mg t.i.d. for periods ranging from 2 to 7 days. Osteomyelitis of the jaw was the only infection for which the dosage regimen of metronidazole was not clearly described.</p><p><strong>Conclusion: </strong>Evidence from the databases searched support the view that OMM has clinical efficacy in the treatment of specific OAIs namely pericoronitis and necrotizing oral infections in immune-competent and immune-compromised patients. The evidence does not support the use of OMM in \"deep tissue\" infections such as osteomyelitis, and odontogenic infections such as acute apical infection and cellulitis. Clinical trials are warranted to determine the efficacy of OMM in comparison with other antibiotic regimens.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"517-524"},"PeriodicalIF":0.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906609","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":"A case of a geriatric patient with thrombocytopenia after partial recovery from COVID-19.","authors":"Yukako Hayashi, Kenji Momo, Mutsumi Ando, Hiroaki Koya, Tsutomu Nagai, Kazuki Shinmura, Issei Tokimatsu, Yasushi Akutsu, Masahiro Kurosawa","doi":"10.5414/CP204664","DOIUrl":"10.5414/CP204664","url":null,"abstract":"<p><p>The global emergence of -COVID-19 has prompted rapid therapeutic and vaccine advancements; however, clinical evidence remains limited. With around a 50% fatality rate for COVID-19 patients with acute respiratory distress syndrome (ARDS), early intervention is crucial. This report details a severe case of post-COVID-19 thrombocytopenia in a 79-year-old man and emphasizes its critical nature. Despite negative initial COVID-19 test results, subsequent positive results led to treatment initiation, and severe thrombocytopenia persisted resulting in bleeding complications and death. Recognized as a hematological manifestation of COVID-19, thrombocytopenia in this geriatric patient highlights the need for extended post-COVID-19 monitoring and management. This underscores the importance of vigilance and timely intervention, especially in vulnerable populations, and emphasizes the need for further research to understand the intricate relationship between COVID-19 and thrombocytopenia.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"538-542"},"PeriodicalIF":0.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140000","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":"Bioequivalence study of two formulations of afatinib dimaleate tablets in healthy subjects under fasting conditions: A randomized, open-label, single-dose, crossover trial.","authors":"Yanping Liu, Lang Lü, Man Xu, Juanmin Tao, Yuping Ning, Yan Shi, Yanfen Dong, Qingqing Cao, Jun Ma, Yan Qiu","doi":"10.5414/CP204514","DOIUrl":"10.5414/CP204514","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the bioequivalence of two different afatinib dimaleate formulations in healthy Chinese subjects under fasting conditions and to assess their pharmacokinetic and safety profiles.</p><p><strong>Materials and methods: </strong>This randomized, open-label, 2-period, crossover, bioequivalence study included 32 healthy Chinese subjects. The subjects were assigned to receive a single 40-mg dose of generic or brand-named afatinib dimaleate tablet. Blood samples were collected pre-dose and up to 120 hours after dosing. Healthy subjects orally took the trial preparation (T) (afatinib maleate tablets developed by Jiangxi Shanxiang Pharmaceutical Co., Ltd., Gan Zhou, China) and the reference preparation (R) (afatinib maleate tablets developed by Boehringer Ingelheim Pharma GmbH & Co., Ingelheim, Germany) under fasting conditions in the appropriate period according to the randomization. We measured the blood concentrations, calculated the pharmacokinetic parameters of the two preparations in the human body, and evaluated whether formulations were bioequivalent. Safety of the preparations in healthy subjects was monitored during the whole trial. Safety assessment was conducted by vital signs, physical examination, laboratory examination, and 12-lead electrocardiogram during the study, i.e., from the time the subject received the test drug to the end of the last visit.</p><p><strong>Results: </strong>Under fasting conditions, the 90% confidence intervals (CIs) of the geometric mean ratios of the test/reference for afatinib dimaleate were 93.34 - 103.92% for AUC_0-t, 90.26 - 105.52% for C_max, and 93.49 - 104.05% for AUC_0-∞.</p><p><strong>Conclusion: </strong>The 90% CI for the geometric mean ratios (test/reference) of C_max, AUC_0-t, and AUC_0-∞ were within the range of 80.00 - 125.00%, indicating that the test formulation was equivalent to the reference formulation in healthy Chinese subjects under fasting conditions. Both products were similar in terms of safety.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"479-485"},"PeriodicalIF":0.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999825","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":"Pulmonary fibrosis insights and therapy targets from disease models and administration of the lipophilic diterpene, sodium tanshinone IIA sulfonate: Review and meta-analysis.","authors":"Li-Ying Peng, Jun-Jun Shi, Yue Liang, Yang Li, Yan Tang, Tuo Kai, Andong Yang, Zi-Yue Xiong","doi":"10.5414/CP204622","DOIUrl":"10.5414/CP204622","url":null,"abstract":"<p><p>Pulmonary fibrosis (PF) is a chronic and progressive pulmonary interstitial disease of unknown etiology and is also a sequela in severe patients with the Coronavirus Disease 2019 (COVID-19). Seven databases were systematically searched to evaluate the preclinical evidence of Tanshinone IIA (Tan IIA) on PF. The quality of the included studies was assessed using a 10-item risk of bias tool, and data were analyzed using RevMan 5.3 software. 22 experiments from 12 studies on a total of 248 animals were included. The results showed that PF phenotype, such as fibrotic score, collagen I (Col-I), collagen III (Col-III), hydroxyproline (Hyp), in the group treated with Tan IIA were significantly lower than those in the model group (p < 0.00001). The potential mechanisms of Tan IIA improvement of PF involve reducing inflammation, antioxidation, and suppressing activation of transforming growth factor beta 1 (TGF-β1). The subgroup analysis of different models, different rat species, and different dosage time showed significant reduction in fibrotic scores and Hyp levels with Tan IIA. The preclinical evidence indicated that Tan IIA might be a potent and promising agent for PF, but this conclusion should be further confirmed with more research.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"460-478"},"PeriodicalIF":0.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906610","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}