{"title":"Treatment of severe psoriasis in a hospice care patient using secukinumab, an inhibitor of interleukin-17A expression: Treatment response and changes in quality of life.","authors":"Yu Zhou, Xueting Ma, Hong Guo, Shaokai Zhang","doi":"10.5414/CP204787","DOIUrl":"https://doi.org/10.5414/CP204787","url":null,"abstract":"<p><p>Secukinumab, a fully human monoclonal antibody that antagonizes interleukin-17A (IL-17A), has proven efficacious in the management of moderate to severe plaque psoriasis. Secukinumab has established itself as an effective treatment for plaque psoriasis, offering rapid and sustained symptom improvement. However, more research is warranted to assess its efficacy and safety in elderly patients, where clinical data is currently lacking. We describe an 84-year-old female presented with stable angina pectoris needed to be hospice cared. She had more than 30 years history of plaque psoriasis. The patient underwent treatment with secukinumab for two weeks. The skin lesions had been decreased rapidly and this greatly improved quality life of this patient. We report the clinical use of secukinumab in the treatment of elderly psoriasis and biologicals may be a new strategy for hospice care of patients with psoriasis.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997986","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":"Prediction of hyperkalemia occurrence in patients using co-trimoxazole: Clinical adjustment of a Markov model.","authors":"Fumiya Watanabe, Toshinori Hirai, Chihiro Shiraishi, Ken Tasaka, Takuya Iwamoto, Kazuhiko Hanada","doi":"10.5414/CP204681","DOIUrl":"10.5414/CP204681","url":null,"abstract":"<p><strong>Objective: </strong>Predicting the occurrence of hyperkalemia in patients undergoing co-trimoxazole treatment for Pneumocystis pneumonia is critical. However, other factors besides drug exposure affect serum potassium levels, and various interventions are often used to treat hyperkalemia in clinical practice. Therefore, we aimed to develop a Markov model to predict the risk of hyperkalemia under various intervention conditions.</p><p><strong>Materials and methods: </strong>This was a retrospective, observational study. Information on daily dose of co-trimoxazole and hyperkalemia events was obtained from adult patients administered oral co-trimoxazole between 2015 and 2020 at Mie University Hospital (Mie, Japan). A Markov model with an intermediate layer was applied using NONMEM. The drug-effect model was assumed to have a maximum effective model. Bootstrapping and visual predictive checks were used to assess model validity.</p><p><strong>Results: </strong>A total of 271 patients with 4039 observations of potassium levels were included. Baseline serum potassium level was a significant covariate of drug response. The successful bootstrap completion rate was 99.5%, and each parameter estimate was consistent with the bootstrap median; therefore, the model was sufficiently robust.</p><p><strong>Conclusion: </strong>The Markov model, including an intermediate layer, provides a robust framework for predicting the risk of hyperkalemia, even in datasets where post-onset interventions vary from patient to patient. Thus, it is postulated that higher baseline potassium levels increase hyperkalemia.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"190-196"},"PeriodicalIF":0.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596964","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}
Xiaoming Wu, Linyi Hou, Jing Liu, Jing Hao, Chang Liu, Yan Hu, Qiang He
{"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":"<p><strong>Background: </strong>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.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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":"220-238"},"PeriodicalIF":0.9,"publicationDate":"2025-05-01","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":"Taken from the Radio Times newspaper (U.K.) December 18, 1931.","authors":"Barrington G Woodcock-Kloberdanz","doi":"10.5414/CPP63177","DOIUrl":"10.5414/CPP63177","url":null,"abstract":"","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"177-178"},"PeriodicalIF":0.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730010","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":"Nano and liposome cancer chemotherapy: A review of advances in drug delivery with applications.","authors":"Lianmei Zhang, Xinglin Jin","doi":"10.5414/CP204715","DOIUrl":"10.5414/CP204715","url":null,"abstract":"<p><p>The high incidence of malignant tumors continues to pose a significant threat to public health. In recent years, there have been notable advancements in tumor treatment methods, leading to substantial changes in the concepts and clinical approaches to treatment. The primary clinical methods for treating malignant tumors currently include surgical resection, radiation therapy, and chemotherapy. Among these, chemotherapy is one of the most crucial and comprehensive treatment strategies. The rapid progress in nanoscience has fostered the development of nanocarrier compounds and their clinical applications in disease treatment. Notably, nanomedicines, including goserelin sustained-release implants, doxorubicin liposomes, albumin-bound paclitaxel, and paclitaxel liposomes, have been effectively utilized in tumor treatment in China [<xref-ref>1</xref-ref>]. The article presents a comprehensive overview of recent advancements in utilizing various nanocarriers for combination therapy in tumors. It also examines the clinical application and efficacy of drug delivery carriers. The development of efficient and safe co-delivery systems that facilitate the effective transport and precise release of drugs within the cancerous tissues while also elucidating the internalization of nanoparticles into tumor cells and their functional mechanisms represents critical areas for future research. Concurrently, advancements in nanocarriers and tumor treatment are anticipated to yield superior therapeutic outcomes and improved quality of life for cancer patients.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"208-216"},"PeriodicalIF":0.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673834","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":"197-207"},"PeriodicalIF":0.9,"publicationDate":"2025-05-01","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}
Zhen Lu, Xiaoyan Huang, Yingjuan Ou, Qinbo Wang, Qirong Tan
{"title":"Cost-utility analysis of pembrolizumab versus nivolumab in the treatment of metastatic colorectal cancer from the perspective of the healthcare payer.","authors":"Zhen Lu, Xiaoyan Huang, Yingjuan Ou, Qinbo Wang, Qirong Tan","doi":"10.5414/CP204665","DOIUrl":"10.5414/CP204665","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is a malignant tumor with the third highest incidence worldwide. The comprehensive economic evaluation of programmed cell death protein-1 inhibitors in China, however, has not yet been carried out. The aim of this study is to assess the cost-utility of pembrolizumab and nivolumab in the treatment of metastatic colorectal cancer (mCRC).</p><p><strong>Materials and methods: </strong>A Markov model microsimulation of efficacy and cost-utility analysis (CUA) was carried out, and efficacy and safety data were compared using network meta-analysis. Literature screening and data extraction were performed according to established criteria where the main outcome indicators, complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) were compared between two treatments. The lifetime cost and outcomes of mCRC treatment were estimated, and quality-adjusted life years (-QALYs) and incremental cost-effectiveness ratio (ICER) were used to evaluate the economy of each program.</p><p><strong>Results: </strong>A total of 442 studies were evaluated of which 15, with a total of 798 patients, were included in the analysis. Of these, 13 evaluated PD, and total patients for CR, PR, SD, and PD were 82, 283, 160, and 180 respectively. The corresponding heterogeneity values were (p = 0.13, heterogeneity index as percentage (I<sup>2</sup>) = 29.53%), (p < 0.01, I<sup>2</sup> = 72.55%), (p = 0.03, I<sup>2</sup> = 46.54%), (p < 0.01, I<sup>2</sup> = 80.31%), and (p = 0.13 > 0.05). The proportion of patients classified as CR in the pembrolizumab group was greater than in the nivolumab group (0.105 vs. 0.085). However, the number of patients classified as PR and SD in the nivolumab group exceeded those in the pembrolizumab group. The number of patients classified as PD were similar in the two groups. Combination therapy nivolumab + ipilimumab yielded an incremental gain of 0.04 QALYs at an additional cost of 356,723 ¥. The ICER reached 8,918,075 ¥/QALYs, surpassing three times the per capita gross domestic product (GDP).</p><p><strong>Conclusion: </strong>Both pembrolizumab and nivolumab showed beneficial effects in patients with mCRC. Nivolumab in combination with ipilimumab led to improved progression-free survival, but the values for ICER reached 8,918,075 ¥/QALYs. Treatment of non-resectable or metastatic microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) advanced solid tumors CRC with pembrolizumab alone, in the Chinese population examined, was the most cost-effective, where the willingness-to-pay threshold was 242,928 ¥/QALY (100 ¥ = 13.75 US$ and 12.63 €).</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"179-189"},"PeriodicalIF":0.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596961","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":"Augmented renal clearance in neurosurgical patients receiving vancomycin: Limited prognostic value for the duration of hospitalization, treatment course, fever, and changes in the CSF test and CRP.","authors":"Lu Sun, Yunchuan Sun","doi":"10.5414/CP204743","DOIUrl":"https://doi.org/10.5414/CP204743","url":null,"abstract":"<p><strong>Objective: </strong>In patients with augmented renal clearance (ARC) receiving vancomycin, therapeutic drug monitoring (TDM) is recommended in accordance with the 2020 guidelines. This study was conducted to delineate the profile of ARC and TDM in non-critically ill, non-trauma, non-stroke neurosurgical patients receiving vancomycin, thereby elucidating the additional risk factors and prognostic implications of ARC.</p><p><strong>Materials and methods: </strong>A single-center retrospective review of clinical data was performed from patients who were consecutively admitted to the Neurosurgical Department of Beijing Tongren Hospital, Capital Medical University, Beijing, China, from November 1, 2017, to October 31, 2022, and received vancomycin. 62 patients with a maximum ICU stay of 72 hours were included. ARC was defined as an estimated glomerular filtration rate (eGFR) of > 130 mL/min/1.73m<sup>2</sup> in the main analysis. A difference analysis based on ARC risk factors, correlation analysis, and multiple linear regression was conducted.</p><p><strong>Results: </strong>The eGFR of the total patient cohort was 115.41 ± 13.39 mL/min/1.73m<sup>2</sup> (mean ± SD), whereas 10 patients (16.13%) had eGFRs > 130 mL/min/1.73m<sup>2</sup>. Younger ages and mannitol co-administration were risk factors for ARC, whereas increased eGFR was not associated with prognostic implications for hospital stay, treatment course, fever duration, or duration to normalization of the CSF test or CRP level.</p><p><strong>Conclusion: </strong>A minimum of 16.13% of non-critical, non-trauma, non-stroke neurosurgical patients exhibit ARC. ARC was not associated with anti-infection prognosis. This finding suggests that further evaluation of ARC-guided TDM of these populations is warranted.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999554","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}