Journal of Clinical Pharmacy and Therapeutics最新文献

{"title":"Effectiveness Evaluation of a Graded Pharmaceutical Care Model in Women with Intrahepatic Cholestasis of Pregnancy: A Before-After Study","authors":"Xiaohui Guo,&nbsp;Yuan Zhang,&nbsp;Yike Shen,&nbsp;Mengdi Sheng,&nbsp;Haixia Zhang,&nbsp;Hongliang Mei","doi":"10.1155/2024/8893465","DOIUrl":"https://doi.org/10.1155/2024/8893465","url":null,"abstract":"<div>\u0000 <p><i>Objective</i>. Intrahepatic cholestasis of pregnancy (ICP) significantly impacts the maternal and fetal safety. Research on the role of clinical pharmacists in guiding drug therapy for this condition remains limited. This study aimed to evaluate the effectiveness of graded pharmaceutical care for women with intrahepatic cholestasis of pregnancy and to provide a theoretical foundation for clinical pharmacist services. <i>Study Design</i>. This study comprises a pre-and-post analysis of women with intrahepatic cholestasis of pregnancy (ICP) treated between December 2019 and June 2023 at a tertiary hospital in Jiangsu province. Each group consisted of 102 participants. The control group received standard treatment, while the guardianship group received graded pharmacological care provided by a clinical pharmacist. The effectiveness of pharmacological monitoring by clinical pharmacists was assessed by comparing and analyzing clinical outcome indicators, quality management indicators, safety indicators, and economic factors. <i>Results</i>. The guardianship group exhibited a noteworthy 12.8% reduction in combined adverse pregnancy outcome and more effective management of total prenatal bile acids compared to the control group (16.05 <i>µ</i>mol/L vs. 22.85 <i>µ</i>mol/L, <i>P</i> &lt; 0.05). The guardianship group displayed superior rationalization of therapeutic drugs and medication duration (<i>P</i> &lt; 0.05). The cost-benefit analysis revealed a favorable economic impact concerning medication costs but did not indicate economic significance regarding total inpatient costs. <i>Conclusion</i>. The implementation of a graded pharmaceutical care model by a clinical pharmacist holds the potential to enhance outcomes for women experiencing intrahepatic cholestasis during pregnancy, mitigate adverse pregnancy results, optimize the rational utilization of therapeutic medications, and yield positive economic results.</p>\u0000 </div>","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"2024 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/8893465","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141967382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between Pandemic of COVID-19 and Influenza Vaccine Take-Up in 2020–2021 in Maine et Loire (France)","authors":"Juliette Abline,&nbsp;Anicet Chaslerie,&nbsp;Emmanüele Fabre,&nbsp;Alain Heymans,&nbsp;Pascal Artarit,&nbsp;Sébastien Faure,&nbsp;Samuel Legeay","doi":"10.1155/2024/9981219","DOIUrl":"https://doi.org/10.1155/2024/9981219","url":null,"abstract":"<div>\u0000 <p><i>Background</i>. Take-up of the influenza (flu) vaccination in France is assessed every year by Santé publique France (SPF), a national health agency. In 2020, the pandemic of COVID-19 took place all over the world. With several symptoms known to be similar between flu and COVID-19, we expected to observe a positive association with people’s choice to also take the flu vaccine injection. <i>Methods</i>. Data regarding the flu vaccination for people aged 65 and over were extracted from the French National Health Data System (Système National des Données de Santé—SNDS). A noninterventional multicenter survey in the Department of Maine et Loire, an area in the west of France, was used for assessing the effect of COVID-19 on vaccination intention. <i>Results</i>. The flu vaccine take-up (Maine et Loire, France), among people aged 65 and over, improved since 2017 (54.36% in 2017–18 vs 58.12% in 2020–21). In 2020–21 (concomitant with the COVID-19 pandemic), people got vaccinated earlier than the previous year (peak in weeks 1–2 vs peak in weeks 5–6 in previous campaigns), before a shortage of doses interrupted the 2020–21 campaign. Of the 211 people who answered the survey among the 232 for whom it was proposed, 175 were vaccinated during the 2020–21 flu vaccine campaign. Among them, 29.12% declared they were aware of COVID-19 when receiving the flu vaccine. The most cited reason for taking the vaccination was the need to feel safe from the influenza virus; the second was “awareness of the fact that a virus can be contagious and deadly.” <i>Conclusion</i>. Our study highlights the COVID-19 association perceived by the elderly population (Maine et Loire) on flu vaccination rates. Despite having human consequences, the COVID-19 pandemic seems to be beneficial to flu vaccine take-up and may positively change people’s beliefs and behaviors towards flu vaccination.</p>\u0000 </div>","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"2024 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/9981219","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141968157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Effectiveness and Safety of Fecal Management Systems among Severely Ill Patients Suffering from Fecal Incontinence: A Retrospective Cohort Study","authors":"Xiecheng Zhou,&nbsp;Ying Yue,&nbsp;Lifeng Gong,&nbsp;Huipeng Wang,&nbsp;Zhou Xin,&nbsp;Yuhui Cui,&nbsp;Wenjie Chen,&nbsp;Xin Wang,&nbsp;Jian Shi,&nbsp;Yuankun Cai","doi":"10.1155/2024/7644383","DOIUrl":"https://doi.org/10.1155/2024/7644383","url":null,"abstract":"<div>\u0000 <p><i>Background</i>. Few large-sample studies have examined the use of fecal management systems (FMSs) in intensive care units (ICUs) or evaluated the associated complications. This study aims to assess the effectiveness and safety of FMS for stool diversion in ICU patients with fecal incontinence (FI). <i>Methods</i>. We enrolled 381 FI patients, assigning them to either an FMS group (<i>n</i> = 134), which used a fecal management device, or a usual care (UC) group (<i>n</i> = 247) that received standard care including regular perianal cleaning. <i>Results</i>. The FMS group reported lower incidence and severity of incontinence-associated dermatitis (IAD) and higher Braden Scale scores (10.42 ± 2.77) compared to the UC group (9.71 ± 2.56), indicating reduced pressure ulcer risk. Notably, FMS-associated complications were minimal, with only 5 patients (3.73%) affected; one required surgical intervention for rectal mucosal bleeding. <i>Conclusions</i>. FMS significantly reduced stool-associated skin irritation, lowered the incidence of IAD and pressure injuries, and improved nurses’ convenience compared to UC.</p>\u0000 </div>","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"2024 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/7644383","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141583822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of Tocolytic Agents in Preterm Labor: A Cross-Sectional Analysis from a Chinese Real-World Study from 2016 to 2021","authors":"Haoran Liu,&nbsp;Xianli Wang","doi":"10.1155/2024/3206060","DOIUrl":"https://doi.org/10.1155/2024/3206060","url":null,"abstract":"<div>\u0000 <p><i>What Is Known and Objective</i>. Tocolytic agents are used to prolong gestational age and prevent immediate preterm birth (PTB). This study aims to provide an overview of the use of tocolytics among patients with PTB in China through retrospectively analyzing trends in application, influencing factors, and inappropriate prescriptions. <i>Methods</i>. The prescription data of five tocolytic agents from 2016 to 2021 were extracted from the database of the Hospital Prescription Analysis Cooperation Project. Drug consumption was expressed as number of prescriptions, cost of prescriptions, and DDDs (defined daily doses). Pearson correlation analysis was used to examine the association between DDDs and DDC (defined daily cost). The appropriateness of prescriptions was analyzed in terms of drug dosage form, administration, clinical diagnosis, and combined medication. <i>Results</i>. The total number of tocolytic prescriptions and the total cost of tocolytic agents increased by 6.12% and 387.58%, respectively, over the six-year duration of the study. From 2016 to 2021, the ranking of the number of prescriptions and DDDs of tocolytic agents was magnesium sulfate &gt; ritodrine &gt; nifedipine &gt; indomethacin &gt; atosiban. During the study period, the cost of tocolytic agents increased significantly, which was mainly related to the increased costs of magnesium sulfate in 2017 and atosiban in 2018 and 2019. The ranking of DDCs was atosiban &gt; ritodrine &gt; magnesium sulfate &gt; nifedipine = indomethacin from 2016 to 2021. For atosiban, the DDC was negatively correlated with the DDDs. Inappropriate prescription, which accounted for 14.84% of all prescriptions, was mainly manifested in the inappropriate selection of nifedipine dosage form, low frequency of nifedipine and indomethacin, and overdosing of ritodrine. Furthermore, 22.87% of tocolytic prescriptions remained active after 34 weeks of gestation, and 7.24% of the prescriptions authorized the use of combination drugs, with magnesium sulfate and nifedipine being the most commonly prescribed combination. <i>What Is New and Conclusion</i>. Magnesium sulfate, ritodrine, and nifedipine were the top three tocolytic agents. As the inappropriate use of tocolytic agents continues to persist, it is important to intensify efforts to ensure the safety and the appropriateness of maternal medication.</p>\u0000 </div>","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"2024 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/3206060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141304195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Catechol-O-Methyltransferase (COMT) Val158Met Polymorphism Is Associated with Oxycodone Requirements, Adverse Effects, and Pain Sensitivity in Cancer Patients","authors":"Silu Xu,&nbsp;Nan Wu,&nbsp;Xin Liu,&nbsp;Jiali Zhu,&nbsp;Zhixian Liu","doi":"10.1155/2024/9990112","DOIUrl":"https://doi.org/10.1155/2024/9990112","url":null,"abstract":"<div>\u0000 <p><i>Purpose</i>. Catechol-O-methyltransferase (COMT) participates in the regulation of dopaminergic and adrenergic neurotransmission. COMT Val158Met polymorphism influences the efficacy and safety of opioids, but its association with oxycodone treatment in patients with cancer pain is yet to be elucidated. Hence, this study aimed to investigate the influence of COMT Val158Met polymorphism on oxycodone requirements, drug adverse effects, and pain sensitivity in patients with cancer. <i>Methods</i>. Patients with moderate to severe cancer pain treated with oxycodone were enrolled, of which 101 patients completed the study. All patients were genotyped for COMT Val158Met polymorphism using DNA from blood samples and were categorized into the wild-type group (<i>n</i> = 50) comprising individuals with the Val/Val genotype and the mutant group (<i>n</i> = 51) encompassing those with the Val/Met or Met/Met genotype. Numerical rating scale (NRS) scores, oxycodone requirements, and the incidence of oxycodone-related adverse drug reactions were compared between the two groups. <i>Results</i>. Patients in the mutant group exhibited higher NRS scores (6.18 ± 1.40) before the oxycodone treatment than those in the wild-type (5.48 ± 1.54) group (<i>P</i> = 0.017). Patients in the wild-type group required more oxycodone (96.00 ± 146.19 mg/24 h) than those in the mutant (77.25 ± 83.91 mg/24 h) group (<i>P</i> = 0.0365). The incidence rates of dysuria (2.0% vs. 16.0%, <i>P</i> = 0.016) and fatigue (0.0% vs. 12.0%, <i>P</i> = 0.013) were significantly lower in the mutant group than those in the wild-type group. Moreover, patients with at least one Met allele showed a lower risk of suffering from oxycodone-related side effects than those with the wild homozygote (41.2% vs. 68.0%, <i>P</i> = 0.007). <i>Conclusion</i>. Genetic variations in the COMT Val158Met gene may contribute to variability in the efficacy and safety of oxycodone in cancer pain treatment. The findings from this study emphasize the potential of pharmacogenetics in personalizing pain management. Furthermore, oxycodone therapeutic strategies can be designed based on genetic polymorphisms.</p>\u0000 </div>","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"2024 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/9990112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141264636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating the Immune Microenvironment and Therapeutic Targets in Nasopharyngeal Carcinoma through Bioinformatics","authors":"Shasha He,&nbsp;Yongbo Zheng","doi":"10.1155/2024/4239046","DOIUrl":"https://doi.org/10.1155/2024/4239046","url":null,"abstract":"<div>\u0000 <p><i>Background</i>. Nasopharyngeal carcinoma (NPC), prevalent in East Asia and associated with EBV infection, poses unique challenges due to its complex immunological interactions. This study aims to dissect the molecular and immune mechanisms of NPC, providing a pathway to novel treatments. <i>Methods</i>. Through bioinformatics, we analyzed gene expression and immune cell infiltration in NPC tissues. Differential gene expression profiling, single-cell RNA sequencing, and gene set variation analysis (GSVA) were performed to understand the immune landscape and identify EBV-related molecular changes. <i>Results</i>. The differential gene expression analysis highlighted a diverse immune cell composition, suggesting an intricate immune evasion landscape. GSVA pinpointed pathways linked to tumor immunity and EBV pathogenesis. Notably, the expression of immune checkpoints, such as PD-L1, was significantly associated with NPC, offering a potential target for immunotherapy. <i>Conclusions</i>. Our findings underscore the potential of immunotherapeutic approaches in NPC, particularly those modulating the PD-1/PD-L1 axis. The integration of bioinformatics and immunology in NPC research provides a foundation for personalized medicine and warrants further exploration into combination therapies to enhance treatment efficacy.</p>\u0000 </div>","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"2024 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/4239046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141264635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors Influencing Insulin Adherence among Outpatients with Type 2 Diabetes Mellitus and the Impact of Pharmaceutical Intervention: A Randomized Clinical Trial","authors":"Ting He,&nbsp;Hao Wang,&nbsp;Wen Sun,&nbsp;Lintong Li,&nbsp;Li Li,&nbsp;Cheng Ji","doi":"10.1155/2024/5518977","DOIUrl":"https://doi.org/10.1155/2024/5518977","url":null,"abstract":"<div>\u0000 <p><i>Aims</i>. This study aimed to identify and analyze the factors significantly influencing long-term insulin medication adherence among outpatients and to evaluate whether pharmaceutical interventions targeting these factors can improve patient medication adherence and glycemic control. <i>Methods</i>. A cohort of 180 patients was recruited from a tertiary hospital in Nanjing, China. Factors potentially influencing insulin adherence were scrutinized employing the KAP (knowledge, attitude/belief, and practice) health behavior model. Baseline characteristics were extracted from the hospital information system, while patient knowledge of the disease and medication, medication adherence, medication beliefs, and management self-efficacy were assessed, respectively, using self-developed questionnaires, MMAS-8, C-DMSES, and BMQ scales. Univariate and multivariate analyses were conducted to determine the impact of these factors on insulin adherence. Following this, participants were randomly allocated to either the intervention or control group. The intervention group received three months of weekly telephone sessions and educational interventions targeting facets such as medication knowledge and beliefs, while the control group received standard care. After the intervention, insulin adherence and glycemic control conditions of both groups were collected and re-evaluated. <i>Results</i>. After excluding lost-to-follow-up patients, 152 individuals were analyzed (intervention: 75 and control: 77). Multivariate analyses revealed factors influencing insulin adherence, including age, diabetes duration, health insurance status, HbA1c level, disease and medication knowledge, diabetes management self-efficacy, and medication beliefs (<i>P</i> &lt; 0.05). Before targeted pharmaceutical care, no significant differences existed in insulin adherence, HbA1c levels, management self-efficacy, knowledge, or medication beliefs between intervention and control groups (<i>P</i> &gt; 0.05). However, subsequent pharmaceutical intervention notably improved adherence, HbA1c levels, self-efficacy, knowledge, and medication beliefs (<i>P</i> &lt; 0.05). <i>Conclusion</i>. This study examines the impact of glycemic control, health insurance status, management self-efficacy, level of knowledge, and medication beliefs on improving insulin medication adherence in patients with type 2 diabetes mellitus. Targeted pharmaceutical intervention can enhance medication adherence, improve glucose control, and promote rational insulin use. This trial is registered with ChiCTR2300074444.</p>\u0000 </div>","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"2024 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/5518977","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141246106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioequivalence and Safety of Two Formulations of Tofacitinib Citrate Tablets in Healthy Chinese Volunteers under Fasting and Fed Conditions: Randomized, Open-Label, 2-Period, Single-Dose, Crossover Trials","authors":"Yanping Liu,&nbsp;Yuping Ning,&nbsp;Yan Shi,&nbsp;Man Xu,&nbsp;Juanmin Tao,&nbsp;Yafen Dong,&nbsp;Jun Ma,&nbsp;Yan Qiu","doi":"10.1155/2024/7914586","DOIUrl":"10.1155/2024/7914586","url":null,"abstract":"<div>\u0000 <p><i>Purpose</i>. To evaluate the bioequivalence of two different tofacitinib citrate tablets formulations among healthy Chinese subjects under fasting and fed conditions and to observe the safety of test preparation and reference preparation in healthy subjects. <i>Method</i>. This randomized, open-label, 2-period, crossover, bioequivalence study included 64 healthy Chinese subjects (fasting: <i>n</i> = 32, fed: <i>n</i> = 32). The subjects were assigned to receive a single 5-mg dose of the test or a reference tofacitinib citrate tablets. Blood samples were collected at predose and up to 24 hours after dosing. Area under the plasma concentration time curve from zero to the last measurable concentration (AUC_0-<i>t</i>), the area from time zero to infinite (AUC_0-∞), and maximum plasma concentration (<i>C</i>_max) were used for bioequivalence assessment. Safety assessment was conducted by vital signs, physical examination, laboratory examination, and 12-lead electrocardiogram during the study, from the time the subject receiving the test drug to the end of the last visit. <i>Results</i>. Under fed condition, the 90% CIs of the geometric mean ratios of the test/reference for tofacitinib citrate tablets were 98.40–104.16% for AUC_0-<i>t</i>, 89.96–116.70% for <i>C</i>_max, and 98.50–104.15% for AUC_0-∞. Under fasting condition, the 90% CIs of the geometric mean ratios of the test/reference for tofacitinib citrate tablets were 93.65–101.60% for AUC_0-<i>t</i>, 90.06–109.15% for <i>C</i>_max, and 93.88–101.51% for AUC_0-∞. There were no serious events. <i>Conclusion</i>. The 90% CI for the geometric mean ratio (test/reference) of <i>C</i>_max, AUC_0-<i>t</i>, 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 both fasting and fed conditions. They are similar in terms of safety. This trial is registered with CTR20190366.</p>\u0000 </div>","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"2024 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/7914586","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141106627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Echinatin Inhibits Oxidative Stress and Inflammatory Processes in Trophoblast Cells by Inhibiting TLR4-MyD88-NF-κB Pathway in Preeclampsia","authors":"Xiangyun Deng,&nbsp;Hu Chen,&nbsp;Yang Zhang,&nbsp;Fengmei Xu,&nbsp;Qian Zhou","doi":"10.1155/2024/2296727","DOIUrl":"10.1155/2024/2296727","url":null,"abstract":"<div>\u0000 <p><i>Background</i>. Preeclampsia (PE) is a common obstetric disorder hallmarked by impaired trophoblast invasion and a skew toward an inflammatory immune response. Echinatin, a flavonoid with established anti-inflammatory, antioxidant, and anticancer activities, may offer therapeutic benefits in PE. Our study aimed to investigate the effect of echinatin on preeclampsia <i>in vitro</i> and <i>in vivo</i> and to reveal the potential molecular mechanism of its action. <i>Methods</i>. Eighteen adult female Sprague Dawley rats were randomized into three experimental groups: a PE model group, a PE + echinatin treatment group, and a PE + echinatin treatment group with TLR4 overexpression. Placental tissue CK7 expression was assessed by immunohistochemistry. TUNEL immunofluorescence staining quantified placental cell apoptosis. Cell viability, proliferation, and migration were evaluated using cell counting kit-8, EdU incorporation, and Transwell assays, respectively. Oxidative stress parameters of malondialdehyde, superoxide dismutase, and glutathione peroxidase were measured. Flow cytometry determined cell apoptosis and intracellular reactive oxygen species (ROS) levels. Western blotting evaluated the expression of proteins related to the TLR4-MyD88-NF-<i>κ</i>B signaling pathway, and the concentrations of TNF-<i>α</i>, IL-6, and IL-18 were measured with ELISA kits. <i>Results</i>. Echinatin mitigated placental damage, reduced apoptosis, and increased CK7 expression. It significantly enhanced HTR-8/SVneo cell viability and migration. Echinatin also counteracted H₂O₂-induced ROS production and cell death in HTR-8/SVneo cells. Moreover, it inhibited the expression of proteins within the TLR4-MyD88-NF-<i>κ</i>B signaling cascade. Overexpression of TLR4 negated echinatin’s protective effects. <i>Conclusion</i>. Echinatin exerts protective effects against oxidative stress and inflammation in PE by targeting the TLR4-MyD88-NF-<i>κ</i>B pathway, suggesting its therapeutic potential for the management of preeclampsia.</p>\u0000 </div>","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"2024 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/2296727","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141122142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population Pharmacokinetic Analysis of Selumetinib and Its N-desmethyl Metabolite in Japanese and Non-Japanese Pediatric Patients with Neurofibromatosis Type 1 and Inoperable Plexiform Neurofibromas","authors":"Takumi Shinbo,&nbsp;Mitsuo Higashimori,&nbsp;Ignacio González-García,&nbsp;Maria Learoyd","doi":"10.1155/2024/4939254","DOIUrl":"https://doi.org/10.1155/2024/4939254","url":null,"abstract":"<p><i>Background</i>. Selumetinib, a mitogen-activated protein kinase kinase 1/2 inhibitor, has been approved in several countries and regions, including Japan, for the treatment of pediatric patients with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas at a body surface area (BSA)-based dose of 25 mg/m² twice daily. The objective of this population pharmacokinetic analysis was to evaluate ethnic sensitivity in the pharmacokinetics of selumetinib and N-desmethyl selumetinib between Japanese and non-Japanese pediatric patients. <i>Methods</i>. This population pharmacokinetic analysis was based on data from 80 pediatric patients enrolled in two clinical trials, one conducted in Japan and one conducted in the United States, comprising 12 Japanese participants and 68 non-Japanese participants. Both clinical trials used BSA-based dosing schemes. A two-compartment model with first-order elimination and sequential zero-order and first-order delayed absorption for selumetinib, combined with a one-compartment model with first-order elimination for N-desmethyl selumetinib, was used for this analysis. Ethnic sensitivity in pharmacokinetics was evaluated by covariate modeling and comparison of model-predicted exposures. <i>Results</i>. Covariate modeling showed that BSA had a clinically relevant impact on the pharmacokinetics of selumetinib. None of the other investigated covariates, such as race, had a significant impact. The predicted exposure in Japanese and non-Japanese patients showed a considerably overlapping distribution, and no clinically relevant difference in exposure was apparent. <i>Conclusions</i>. These findings support the use of the same BSA-based dosing regimen for Japanese and non-Japanese pediatric patients with neurofibromatosis type 1 and inoperable plexiform neurofibromas. Subsequent to this analysis, selumetinib was approved at the BSA-based dose of 25 mg/m² in Japan, which is consistent with the recommended dosage and administration in other regions and countries. This analysis used data from trial registered with NCT04495127, and NCT01362803.</p>","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"2024 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141164921","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}