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Objectives: Coronary artery bypass grafting (CABG) is essential for treating coronary artery disease, with postoperative aspirin crucial to prevent graft restenosis. However, its gastrointestinal side effects may limit tolerability in some patients. Indobufen presents a potential alternative, but its safety and efficacy need further validation. This study aimed to compare the efficacy and safety of indobufen versus aspirin in patients' post-CABG. Methods: This retrospective observational study included 39 patients who underwent CABG at two centers from January to December 2023. Patients were retrospectively assigned to two groups based on the antiplatelet therapy they received: the indobufen group (n = 19) and the aspirin group (n = 20). The primary endpoint was a composite of non-fatal myocardial infarction, stroke, and revascularization due to acute coronary syndrome in the intention-to-treat population. Postoperative data on platelet count, hemoglobin, D-dimer, activated partial thromboplastin time (APTT), and hospital stay length were collected. Transfusion rate, bleeding, thrombotic events, and gastrointestinal adverse reactions were compared between the two groups. Results: Over the 8-to-18-month follow-up period, 5 patients (25%) in the aspirin group reached the primary endpoint, while none in the indobufen group did, a difference that was statistically significant (p = 0.02). Although the rates of non-fatal myocardial infarction, revascularization, stroke, and thrombotic events were higher in the aspirin group, these differences did not reach statistical significance. Importantly, the total bleeding events were markedly lower in the indobufen group (15.79% vs. 55%, p = 0.011), with major bleeding events also significantly reduced in the indobufen group (0% vs. 20%, p = 0.04). Both groups showed no significant differences were observed in postoperative hospital stay, hemoglobin, and D-dimer levels between the groups. However, the indobufen group demonstrated significantly lower platelet count and APTT. The average daily cost of indobufen was 27.8 times higher than that of aspirin. Conclusion: Indobufen demonstrates a comparable antiplatelet effect to aspirin and offers significant advantages in reducing gastrointestinal adverse reactions and bleeding risk. It can be considered a preferable alternative for patients who cannot tolerate or have contraindications to aspirin. Further large-scale clinical trials are needed to confirm its potential as the first-choice antiplatelet therapy post-CABG. [ABSTRACT FROM AUTHOR]

Objectives: Coronary artery bypass grafting (CABG) is essential for treating coronary artery disease, with postoperative aspirin crucial to prevent graft restenosis. However, its gastrointestinal side effects may limit tolerability in some patients. Indobufen presents a potential alternative, but its safety and efficacy need further validation. This study aimed to compare the efficacy and safety of indobufen versus aspirin in patients’ post-CABG. Methods: This retrospective observational study included 39 patients who underwent CABG at two centers from January to December 2023. Patients were retrospectively assigned to two groups based on the antiplatelet therapy they received: the indobufen group (n = 19) and the aspirin group (n = 20). The primary endpoint was a composite of non-fatal myocardial infarction, stroke, and revascularization due to acute coronary syndrome in the intention-to-treat population. Postoperative data on platelet count, hemoglobin, D-dimer, activated partial thromboplastin time (APTT), and hospital stay length were collected. Transfusion rate, bleeding, thrombotic events, and gastrointestinal adverse reactions were compared between the two groups. Results: Over the 8-to-18-month follow-up period, 5 patients (25%) in the aspirin group reached the primary endpoint, while none in the indobufen group did, a difference that was statistically significant (p = 0.02). Although the rates of nonfatal myocardial infarction, revascularization, stroke, and thrombotic events were higher in the aspirin group, these differences did not reach statistical significance. Importantly, the total bleeding events were markedly lower in the indobufen group (15.79% vs. 55%, p = 0.011), with major bleeding events also significantly reduced in the indobufen group (0% vs. 20%, p = 0.04). Both groups showed no significant differences were observed in postoperative hospital stay, hemoglobin, and D-dimer levels between the groups. However, the indobufen group demonstrated significantly lower platelet count and APTT. The average daily cost of indobufen was 27.8 times higher than that of aspirin. Conclusion: Indobufen demonstrates a comparable antiplatelet effect to aspirin and offers significant advantages in reducing gastrointestinal adverse reactions and bleeding risk. It can be considered a preferable alternative for patients who cannot tolerate or have contraindications to aspirin. Further large-scale clinical trials are needed to confirm its potential as the first-choice antiplatelet therapy post-CABG. [ABSTRACT FROM AUTHOR]

ObjectiveThis meta-analysis aims to evaluate the safety and efficacy of indobufen in the treatment of cardiovascular diseases, cerebrovascular diseases, and thromboembolic disorders. The primary focus is on the incidence of major adverse cardiovascular events (MACE), thrombosis, bleeding events, and adverse reactions. The results are intended to provide a reference for the clinical application of indobufen and suggest directions for further large-scale, multi-center, prospective studies.MethodsThis review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search was conducted in PubMed, Embase, Web of Science, and the Cochrane Library databases to identify all relevant studies on indobufen. Twelve trials, all randomized controlled trials (RCTs), met the inclusion criteria. The results were presented as risk ratios (RR) with 95% confidence intervals (CI), and meta-analysis was performed using RevMan 5.3 and Stata 18.0 software.ResultsThe meta-analysis included 12 randomized controlled trials. Regarding safety, indobufen showed superior clinical outcomes compared to other antiplatelet agents regarding bleeding events, gastrointestinal adverse reactions, and overall adverse reactions, with these differences being more pronounced in cardiovascular diseases. However, the effects of both treatments on efficacy outcomes, including MACE, myocardial infarction, angina, mortality, and thrombotic events, were similar. For stroke events, particularly in patients with cerebrovascular diseases, the use of indobufen was associated with some risk.ConclusionIndobufen is associated with a lower risk of adverse reactions and bleeding, making it a viable option for patients at risk of bleeding or adverse effects, particularly in those with cardiovascular diseases. However, compared to anticoagulants such as aspirin and clopidogrel, indobufen has a shorter history of use, and its evidence base is relatively limited, highlighting the need for further research. Currently, indobufen is widely used in secondary cardiovascular and cerebrovascular prevention and provides some guidance for antiplatelet therapy in patients with gastrointestinal discomfort or bleeding risk. However, due to the potential risks in MACE, stroke, and other events, further clinical trials are needed to assess the clinical applicability of indobufen.Systematic Review Registrationhttps://www.crd.york.ac.uk/, identifier (CRD42024587938).

Currently, the standard treatment for patients who have undergone percutaneous coronary intervention (PCI) following acute myocardial infarction (MI) involves dual antiplatelet therapy (DAPT) with a combination of aspirin and a potent P2Y12 receptor inhibitor. However, the potential benefits of aspirin were partially constrained by the intolerance of some patients. The safety and efficacy of indobufen, an alternative antiplatelet agents to aspirin, in patients with AMI after PCI are yet to be thoroughly investigated.This retrospective study was conducted at a single center and utilized propensity score matching. The enrollment spanned from January 2019 to June 2022, incorporating patients with AMI after PCI. The participants were categorized into two groups based on discharged prescriptions: the aspirin DAPT group and the indobufen DAPT group. The primary endpoint focused on net adverse clinical event (NACE), defined as a composite outcome, including cardiac death, recurrence of MI, definite or probable stent thrombosis (ST), target lesion revascularization (TLR), ischemic stroke and Bleeding Academic Research Consortium (BARC) criteria type 2, 3, or 5. All the patients underwent a one-year follow-up period.A total of 1451 patients were enrolled in this study, with 258 assigned to the indobufen DAPT group and 1193 to the aspirin DAPT group. Following 1:1 propensity score matching, 224 patients were retained in each group. In the indobufen DAPT group, 58 individuals (25.9%) experienced the primary endpoint within one year, compared to 52 individuals (23.2%) in the aspirin DAPT group (HR 1.128, 95% CI 0.776–1.639, p = .527). Specifically, no significant differences were observed in either the efficacy endpoint (MACCE, 20.1% vs. 14.7%, HR 1.392, 95% CI 0.893–2.170, p = .146) or the safety endpoint (BARC 2,3 or 5, 8.04% vs. 10.30%, HR 0.779, p = .427). These findings remained consistent at 1, 3, or 6 months. Additionally, the incidence of gastrointestinal symptoms were significantly lower in indobufen DAPT group compared to the aspirin DAPT group (7.1% vs. 14.3%, p = .022).Our research reveals that the efficacy and safety of indobufen are comparable to aspirin in Chinese patients with AMI following PCI. Given the potential advantages of indobufen in alleviating gastrointestinal symptoms, we propose it as a viable alternative for individuals intolerant to aspirin.

Background: Ischemic stroke (IS) is a detrimental neurological disease and IS lacks valuable methods to recover body function. Indobufen (IND) could alleviate IS. However, the possible mechanism remains undefined. Methods: SH-SY5Y cells were cultured under the oxygen-glucose deprivation/reoxygenation (OGD/R) environment and then were treated with small interfering RNA (siRNA) of NRF2 and ATG5. The influence of various concentrations of IND (50 μM, 100 μM, 200 μM, and 400 μM) was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide. Levels of superoxide dismutase (SOD) and malonaldehyde (MDA) were examined by ELISA. Reactive oxygen species (ROS) production was determined by DCFH-DA staining. The protein levels of LC3II/LC3I, Beclin1, p62, NRF2, and ATG5 were detected by western blot. Results: IND increased cell viability, while depressed the rate of apoptosis in SH-SY5Y cells of OGD/R environment. IND inhibited autophagy by suppressing the levels of LC3II/LC3I, Beclin1 protein, and increasing p62 protein expression in SH-SY5Y cells of OGD/R environment. IND limited the contents of ROS and MDA, while amplifying the activity of SOD in SH-SY5Y cells with OGD/R exposure. IND also promoted NRF2 expression in OGD/R environment. Conclusion: IND could inhibit autophagy, oxidative stress, and apoptosis in SH-SY5Y cells with OGD/R exposure, further alleviating IS injury by regulating transcription factor NRF2 and inhibiting ATG5 expression. [ABSTRACT FROM AUTHOR]

IntroductionAspirin and indobufen are commonly used therapeutic drugs for the prevention of vascular restenosis (VR) after percutaneous transluminal angioplasty surgery. They both exhibited antiplatelet effects but molecular mechanisms underlying metabolic changes induced by them remain unclear.MethodsIn this study, we collected plasma samples from patients on aspirin medication (n = 5), patients on indobufen medication, patients with no medication after PTA, and healthy controls (CKs) (n = 5). Our investigation aimed to reveal the metabolic processes in patients during vascular restenosis and its amelioration through drug therapy using liquid chromatography-tandem mass spectrometry (LC-MS/MS).ResultsOur data showed significant alterations in amino acid and choline metabolism in patients without medication after PTA. Aspirin and indobufen were able to regulate these metabolic pathways to alleviate VR symptoms. We identified several characteristic amino acids, including pro-leu, L-citrulline, his-glu, and L-glutamate, as important biomarkers for VR assessment in patients without medication after PTA. A total of 17 and 4 metabolites involved in arginine and phenylalanine metabolism were specifically induced by aspirin and indobufen, respectively. Their expression levels were significantly regulated by aspirin or indobufen, nearly reaching normal levels.DiscussionTaken together, our identification of metabolites involved in metabolic changes affected by aspirin and indobufen medication enhances the understanding of VR pathology after PTA. This may help identify early diagnostic biomarkers and therapeutic targets

PurposeThis meta-analysis aimed to compare the safety and efficacy of aspirin and indobufen in patients with coronary heart disease. The primary focus was on the incidence of cardiovascular events, bleeding events, and gastrointestinal reactions. Given the relatively limited research on indobufen, this study utilized aspirin as a control drug and employed meta-analysis to integrate existing clinical studies. The goal was to provide a reference for the clinical use of indobufen and to suggest directions for further largescale, multicenter prospective studies.MethodsThis review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We conducted a comprehensive search of the PubMed, EMBASE, WOS, and Cochrane Library databases to identify all relevant literature on indobufen. A total of nine trials met the inclusion criteria, encompassing seven randomized controlled trails (RCTs) and two retrospective studies. Categorical variables were analyzed using odds ratio and random effects models.ResultsThe meta-analysis included nine trials, comprising seven RCTs and two retrospective studies. The pooled results indicated that indobufen significantly reduced the incidence of minor bleeding events, and gastrointestinal discomfort compared to aspirin. However, both drugs had similar effects on the incidence of recurrent angina pectoris, myocardial infarction and mortality due to coronary heart disease.ConclusionIndobufen was associated with fewer gastrointestinal reactions and a low risk of bleeding, making it a viable option for patients with high-risk factors for bleeding and gastric ulcers. Despite this, indobufen's short history and limited evidence base compared to aspirin highlight the need for further research. Aspirin remains widely available, cost-effective, and the preferred drug for the primary and secondary prevention of cardiovascular and cerebrovascular diseases. Indobufen or other antiplatelet agents should only be considered when aspirin is not tolerated or contraindicated. Further clinical trials are necessary to determine whether indobufen can replace aspirin.Systematic Review Registrationhttps://www.crd.york.ac.uk/, identifier [CRD42024523477].

Abstract Background Indobufen is widely used in patients with aspirin intolerance in East Asia. The OPTION trial launched by our cardiac center examined the performance of indobufen based dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). However, the vast majority of patients with acute coronary syndrome (ACS) and aspirin intolerance were excluded. We aimed to explore this question in a real-world population. Methods Patients enrolled in the ASPIRATION registry were grouped according to the DAPT strategy that they received after PCI. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE) and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. Propensity score matching (PSM) was adopted for confounder adjustment. Results A total of 7135 patients were reviewed. After one-year follow-up, the indobufen group was associated with the same risk of MACCE versus the aspirin group after PSM (6.5% vs. 6.5%, hazard ratio [HR] = 0.99, 95% confidence interval [CI] = 0.65 to 1.52, P = 0.978). However, BARC type 2, 3, or 5 bleeding was significantly reduced (3.0% vs. 11.9%, HR = 0.24, 95% CI = 0.15 to 0.40, P

Background: Indobufen is widely used in patients with aspirin intolerance in East Asia. The OPTION trial launched by our cardiac center examined the performance of indobufen based dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). However, the vast majority of patients with acute coronary syndrome (ACS) and aspirin intolerance were excluded. We aimed to explore this question in a real-world population. Methods: Patients enrolled in the ASPIRATION registry were grouped according to the DAPT strategy that they received after PCI. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE) and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. Propensity score matching (PSM) was adopted for confounder adjustment. Results: A total of 7135 patients were reviewed. After one-year follow-up, the indobufen group was associated with the same risk of MACCE versus the aspirin group after PSM (6.5% vs. 6.5%, hazard ratio [HR] = 0.99, 95% confidence interval [CI] = 0.65 to 1.52, P = 0.978). However, BARC type 2, 3, or 5 bleeding was significantly reduced (3.0% vs. 11.9%, HR = 0.24, 95% CI = 0.15 to 0.40, P < 0.001). These results were generally consistent across different subgroups including aspirin intolerance, except that indobufen appeared to increase the risk of MACCE in patients with ACS. Conclusions: Indobufen shared the same risk of MACCE but a lower risk of bleeding after PCI versus aspirin from a real-world perspective. Due to the observational nature of the current analysis, future studies are still warranted to further evaluate the efficacy of indobufen based DAPT, especially in patients with ACS. Trial registration: Chinese Clinical Trial Register (https://www.chictr.org.cn); Number: ChiCTR2300067274. [ABSTRACT FROM AUTHOR]

Copyright of Practical Pharmacy & Clinical Remedies is the property of Editorial Department of Practical Pharmacy & Clinical Remedies and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

OBJECTIVE: To evaluate the efficacy and safety of indobufen in the prevention of venous thrombosis. METHODS: PubMed, Embase, the Cochrane Library, ClinicalTrial. gov, CNKI, Wanfang Data and CBM were searched electronically for randomized controlled trial (RCT) of indobufen in the prevention of venous thrombosis (the interventions were indobuprofen alone or in combination with other conventional drugs, while the control measures were other positive control drugs alone or in combination with other conventional drugs) up to May 2023. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of the included literature. Meta-analysis was performed by using RevMan 5. 3 software. RESULTS: A total of 15 RCT with 2 164 patients were included. There were 1 117 patients in the indobufen group and 1 047 patients in the control group. Efficacy results showed that the there was sufficient evidence-based evidence for Meta-analysis of indobufen in thromboprophylaxis of atrial fibrillation (AF), thromboprophylaxis after major orthopedic surgery, and thromboprophylaxis of idiopathic model nephropathy, and the results were not worse than warfarin or other anticoagulants. In the prevention of thrombosis after AF combined with ischemic cardio-cerebrovascular disease, nephrotic syndrome and superficial varices of lower extremities, indobufen also had some evidence, yet it was not enough for quantitative analysis. Safety outcomes showed that the incidences of bleeding (RR = 0. 18,95% CI = 0. 09- 0. 38, P<0. 000 01) and minor bleeding (RR = 0. 17, 95% CI = 0. 05-0. 52, P = 0. 002) induced by indobufen in prevention of AF thrombosiswas were significantly lower than those in warfarin, with statistically significant differences. CONCLUSIONS: Indobufen has accumulated a certain amount of evidence-based evidence in the prevention of venous thrombosis. The clinical efficacy of indobufen in the prevention of venous thrombosis is not inferior to that of conventional therapy, and the safety of indobufen is better. [ABSTRACT FROM AUTHOR]

After coronary drug-eluting stent (DES) implantation, dual antiplatelet therapy (DAPT, usually aspirin in combination with a P2Y12 inhibitor) is necessary. However, older patients are prone to aspirin intolerance or resistance. Indobufen has been reported as an ideal alternative to aspirin. To evaluate the clinical efficacy and safety of indobufen-based DAPT in this population, a total of 251 older patients (aged ≥65 years) undergoing coronary DES implantation in a tertiary healthcare facility in Quzhou, China, were enrolled, of which 110 received indobufen-based DAPT and 141 received aspirin-based DAPT. Baseline data, adverse reactions, adverse events, angina attacks, and repeated revascularization during 1-year follow-up were collected. At 1-year follow-up, creatinine, and left ventricular ejection fraction levels in the indobufen group were higher than those in the aspirin group, whereas estimated glomerular filtration rate levels were lower than those in the aspirin group. No significant difference in the incidence of adverse reactions or adverse events was found between the two groups. At 1-year follow-up, the incidence of angina in the indobufen group was significantly lower than that in the aspirin group, and the repeated revascularization rate was lower than that in the aspirin group. Indobufen-based DAPT was beneficial in avoiding repeated revascularizations (odds ratio 0.433, 95% CI 0.229-0.821, P = 0.010). These findings highlight that, for older patients who underwent coronary DES implantation, indobufen-based DAPT may be a better choice, which can effectively improve patients' symptoms and prognosis. However, application to older patients with potential renal insufficiency requires caution. [ABSTRACT FROM AUTHOR]

Currently, the standard treatment for patients who have undergone percutaneous coronary intervention (PCI) following acute myocardial infarction (MI) involves dual antiplatelet therapy (DAPT) with a combination of aspirin and a potent P2Y12 receptor inhibitor. However, the potential benefits of aspirin were partially constrained by the intolerance of some patients. The safety and efficacy of indobufen, an alternative antiplatelet agents to aspirin, in patients with AMI after PCI are yet to be thoroughly investigated. This retrospective study was conducted at a single center and utilized propensity score matching. The enrollment spanned from January 2019 to June 2022, incorporating patients with AMI after PCI. The participants were categorized into two groups based on discharged prescriptions: the aspirin DAPT group and the indobufen DAPT group. The primary endpoint focused on net adverse clinical event (NACE), defined as a composite outcome, including cardiac death, recurrence of MI, definite or probable stent thrombosis (ST), target lesion revascularization (TLR), ischemic stroke and Bleeding Academic Research Consortium (BARC) criteria type 2, 3, or 5. All the patients underwent a one-year follow-up period. A total of 1451 patients were enrolled in this study, with 258 assigned to the indobufen DAPT group and 1193 to the aspirin DAPT group. Following 1:1 propensity score matching, 224 patients were retained in each group. In the indobufen DAPT group, 58 individuals (25.9%) experienced the primary endpoint within one year, compared to 52 individuals (23.2%) in the aspirin DAPT group (HR 1.128, 95% CI 0.776-1.639, p = .527). Specifically, no significant differences were observed in either the efficacy endpoint (MACCE, 20.1% vs. 14.7%, HR 1.392, 95% CI 0.893-2.170, p = .146) or the safety endpoint (BARC 2,3 or 5, 8.04% vs. 10.30%, HR 0.779, p = .427). These findings remained consistent at 1, 3, or 6 months. Additionally, the incidence of gastrointestinal symptoms were significantly lower in indobufen DAPT group compared to the aspirin DAPT group (7.1% vs. 14.3%, p = .022). Our research reveals that the efficacy and safety of indobufen are comparable to aspirin in Chinese patients with AMI following PCI. Given the potential advantages of indobufen in alleviating gastrointestinal symptoms, we propose it as a viable alternative for individuals intolerant to aspirin. [ABSTRACT FROM AUTHOR]

The risk of thromboembolic events is elevated in patients with nephrotic syndrome, and warfarin use has been associated with an increased risk of bleeding. Indobufen, a selective cyclooxygenase-1 inhibitor, is currently being evaluated for the prevention of thromboembolic events in nephrotic syndrome. This study aimed to compare the efficacy and safety of indobufen with that of warfarin in patients with nephrotic syndrome. This multicenter, randomized, three-arm, open-label, parallel controlled trial involved a total of 180 adult patients with nephrotic syndrome from four centers in China. Patients were randomly assigned to receive 100 mg indobufen (bid), 200 mg indobufen (bid), and 3 mg warfarin (qd) daily for 12 weeks. The primary endpoints included thromboembolic and bleeding events, while laboratory results and adverse events constituted secondary endpoints. No thromboembolic events occurred in the high-/low-dose indobufen and warfarin groups. Moreover, the use of a low dose of indobufen significantly reduced the risk of minor bleeding events compared with warfarin use (2% versus 18%, p <.05). Finally, adverse events were more frequent in warfarin-treated patients. This study found that indobufen therapy provided equivalent effects in preventing thromboembolic events compared with warfarin therapy, while low dose of indobufen was associated with a reduced risk of bleeding events, thus it should be recommended for the prevention of thromboembolic events in clinical practice in patients with nephrotic syndrome. ChiCTR-IPR-17013428. [ABSTRACT FROM AUTHOR]

Commonly, most oral non-steroidal anti-inflammatory drugs (NSAIDs) have known gastric adverse reactions due to their long-term and high dose administration. In this study, a novel liquid sustained-release system based on multiple-unit in situ hydrogel beads was designed to address this issue. The system is composed of sodium alginate (SA), gellan gum (GG), zinc oxide (ZnO), and magnesium oxide (MgO). Furthermore, indobufen was loaded into the system to evaluate its gastric mucosal protection effect. This effect can be attributed to the topical antacid, pepsin inhibition, and sustained drug release properties of the system. It was proven that the stored solid gel system could undergo a "solid to liquid" transition after shaking. Once swallowed, the liquid gel could disperse well in the stomach as hydrogel beads. Then, the "liquid to solid" gelation occurred from the exterior to interior of each multiple-unit gel bead, triggered by the release of Zn2+ and Mg2+ from neutralization reactions. The formed gel demonstrated mild antacid effect that lasted for 3 hours and 66.3% pepsin inhibition in vivo. Moreover, the rats treated with the indobufen gel system showed a drug plasma concentration versus time curve with less fluctuation compared to the rats treated with the marketed preparation (YinDuo®) group. The gel system also exhibited an extended T max (6.50 hours) and reduced C max (52.87 μg/mL). Additionally, the gastric mucosal protection of the gel system was verified using three types of peptic gastric ulcer models. These findings suggested that this multiple-unit in situ gel could be a potential oral liquid sustained release delivery system for NSAIDs. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the cost-effectiveness of indobufen combined with ticagrelor versus aspirin combined with ticagrelor for antiplatelet therapy after percutaneous coronary intervention (PCI). METHODS: Markov model was used to simulate the economic outcomes of patients treated with indobufen + ticagrelor and aspirin + ticagrelor for antiplatelet therapy after PCI. Quality-adjusted life years (QALY) was set as the effectiveness measure, the total costs, total effectiveness and incremental cost-effectiveness ratios ( ICER) of two treatment regimens were calculated. RESULTS: Over a 10-year time horizon, the total cost of indobufen + ticagrelor was 172 292. 28 yuan, while the total cost of aspirin + ticagrelor was 169 950. 51 yuan. The QALY gained with indobufen + ticagrelor and aspirin + ticagrelor were 6. 540 and 6. 335, respectively. The ICER of indobufen + ticagrelor to aspirin + ticagrelor was 11 472. 09 yuan / QALY, lower than per capita GDP in China. These results suggested that indobufen+ticagrelor is significantly better than aspirin+ticagrelor in cost-effectiveness. Sensitivity analysis demonstrated that the results of the study were robust and reliable. CONCLUSIONS: Results of the study indicate that indobufen + ticagrelor is more cost-effectiveness than aspirin + ticagrelor under the current economic conditions in China, and can be used as the first selection of antiplatelet therapy for patients after PCI. [ABSTRACT FROM AUTHOR]

临床试验是评估新药或新疗法有效性和安全性最有效的方法，可以提供高质量的循证医学证据。近年来全球的临床试验数量逐渐增加，试验结果为阴性十分常见。当临床试验的主要结果为阴性时，并不一定就意味着研究的失败，研究者还需要多方考虑以便从中找到潜在益处的线索。本文阐述了临床试验主要结局为阴性时需要考虑的12个要点，并以吲哚布芬对比阿司匹林治疗急性缺血性卒中（indobufen versus aspirin in acute ischemic stroke，INSURE）研究为例进行讨论，以期为后续的临床试验设计和结果解读提供经验。 Abstract: Clinical trials are the most effective method for evaluating the efficacy and safety of new drugs or new therapies, and can provide high-quality evidence-based medical evidence. In recent years, the number of clinical trials worldwide increased gradually, negative results from clinical trials are very common. When the main result of a clinical trial is negative, it does not necessarily mean that the study is a failure, and researchers should consider multiple factors to find potential benefits. Therefore, we elaborated in detail the 12 key points to consider, when encountering the negative primary outcome, and discussed by taking indobufen versus aspirin in acute ischemic stroke (INSURE) study as an example provide reference experience for subsequent clinical research design and results interpretation.

After the reaction, the solid was collected by removing the solvent, and the pure compound B 6 b was obtained through washing with dilute hydrochloric acid. The compounds methyl 2-(4-nitrophenyl)butanoate ( B 7 b ), [25] methyl 2-(4-aminophenyl)butanoate ( B 5 b ), [26] methyl 2-(4-(1-oxoisoindolin-2-yl)phenyl)butanoate ( B 6 b ), [24] and 2-(4-(1-oxoisoindolin-2-yl)phenyl)butanoic acid (indobufen), [27] were synthesized in accordance with the methods published. Keywords: indobufen; anticoagulant; diludine; isoindolinone; hectogram-scale EN indobufen anticoagulant diludine isoindolinone hectogram-scale 2543 2546 4 07/31/23 20230817 NES 230817 Graph Isoindolinone is an important structural motif of many natural products [2] and synthetic drugs [5] that exhibit important biological activities such as the anti-inflammatory drug indobufen, the anti-tumor agent lenalidomide, the tumor necrosis factor (TNF- ) production inhibitor DWP205190, and selective metabotropic glutamate receptor (mGluR) 1 allosteric antagonist CFMTI (Figure 1). 2-(4-(1-Oxoisoindolin-2-yl)phenyl)butanoic Acid (Indobufen) To a solution of compound B 6 b (296.7 g, 0.959 mol) were added MeOH (1500 mL) and aq 1 N NaOH (1500 mL). [Extracted from the article]

Clinically, indobufen is widely used for the treatment of antiplatelet aggregation and anticoagulation. Prior studies have discovered that abnormal platelet function can be promptly restored to normal when the drug is stopped. Herein, through the study of the enzyme reaction kinetics, we demonstrated that the inhibitory effect of indobufen on cyclooxygenase-1 (COX-1) was reversible and non-competitive. Specifically, the cyclooxygenase inhibition experiment showed that the level of 6-keto-PGF1α in the gastric mucosa of the indobufen-treated groups was significantly higher than that of the aspirin group (###p < 0.001), indicating a higher level of PGI2 in and a better physiological state of the gastric mucosa. Moreover, the rat gastric ulcer index and mucosal section experiments further confirmed the relief of gastrointestinal irritation and the adverse reaction rate of the indobufen-treated group compared to those of the aspirin group. Furthermore, indobufen was verified to exert reversible inhibitory activity on the heme group of COX-1 and thus reversibly inhibit COX-1 activity. In general, compared with aspirin, the long-term oral administration of indobufen yields a lower risk of gastrointestinal symptoms, such as ulcers. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of indobufen combined with clopidogrel on vascular endo- thelial function, inflammatory factors, and oxidative stress in patients with acute coronary syndrome. Methods This study retrospectively selected 156 patients as the research object who had acute coronary syndrome and underwent PCI in our hospital from June 2020 to March 2022. They were divided into two groups by the number table method, with78 patients in each group. The observation group was treated with indobufen combined with clopidogrel, and the control group was treated with clopidogrel. The efficacy and indicators of patients were compared, and the adverse reactions were recorded. Result The therapeutic effect of the observation group was better than that of the control group (P < 0.05); After treatment, the endothelial function indicators of both groups of patients were significantly improved compared to before treatment (P < 0.05), and the VEGF level in the observation group was higher than that in the control group (P < 0.05), while ET-1 was lower than that in the control group (P < 0.05); After treatment, the inflammatory factors in patients decreased compared to those after treatment (P < 0.05), and the observation group showed hs CRP and TNF-α levels. These levels were significantly lower than those of the control group (P < 0.05); After treatment, the oxidative stress indicators of patients improved compared to before treatment (P < 0.05), and the NO and tNOS indicators in the observation group were significantly higher than those in the control group (P < 0.05), while the malondialdehyde levels were lower than those in the control group (P < 0.05); The incidence of cardiovascular adverse events and bleeding in the observation group after treatment was lower than that in the control group (P < 0.05); There was no statistically significant difference in the incidence of adverse reactions between the two groups (P > 0.05). Conclusion The application of indobufen combined with clopidogrel in the treatment of acute coronary syndrome patients has a definite therapeutic effect that can effectively improve various indicators, reduce the incidence of adverse events, and alleviate inflammation and therefore lead to a low bleeding rate, and good safety, which is worthy of further promotion. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Stroke is the property of Chinese Journal of Stroke Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Clinical Nursing in Practice is the property of Journal of Clinical Nursing in Practice (Editorial Board, Shanghai Jiao Tong University Press) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Dual antiplatelet therapy (DAPT) with aspirin as a background therapy has become the standard care following percutaneous coronary intervention (PCI). However, some adverse non-cardiac effects limited the use of aspirin in clinical practice. Thus, evaluation of pharmacological alternatives to aspirin is attractive. Previous data indicated that indobufen could lessen the unwanted side effects of aspirin while retain the antithrombotic efficacy, but its combination with a P2Y12 inhibitor is still lack of randomized clinical trial (RCT) evidence. Methods: In this randomized, open-label, non-inferiority trial, patients with negative cardiac troponin undergoing coronary drug-eluting stent (DES) implantation were randomly assigned in a 1:1 ratio to receive either indobufen-based DAPT (indobufen 100mg twice a day plus clopidogrel 75mg/d for 12 months) or conventional DAPT (aspirin 100mg/d plus clopidogrel 75mg/d for 12 months). The primary endpoint was a 1-year composite of cardiovascular (CV) death, nonfatal myocardial infarction (MI), ischemic stroke, definite or probable stent thrombosis (ST), or Bleeding Academic Research Consortium (BARC) criteria type 2, 3 or 5 bleeding. The endpoints were adjudicated by an independent Clinical Event Committee. Results: Between January 11, 2018 and October 12, 2020, 4551 patients were randomized in 103 cardiovascular centers: 2258 patients to the indobufen-based DAPT group and 2293 to the conventional DAPT group. The primary endpoint occurred in 101 (4.47%) patients in the indobufen-based DAPT group and 140 (6.11%) patients in the conventional DAPT group (absolute difference -1.63%, pnon-inferiority <0.001; hazard ratio (HR) 0.73, 95% CI 0.56 to 0.94, p=0.015). CV death, nonfatal MI, ischemic stroke and ST were observed in 0.13%, 0.40%, 0.80%, and 0.22% of patients in the indobufen-based DAPT group, and 0.17%, 0.44%, 0.83%, and 0.17% of patients in the conventional DAPT group (all p>0.05). The occurrence of BARC criteria type 2, 3 or 5 bleeding events was lower in the indobufen-based DAPT group compared to the conventional DAPT group (2.97% vs 4.71%, HR 0.63, 95%CI 0.46 to 0.85, p=0.002), with main decrease in type 2 bleeding (1.68% vs 3.49%, HR 0.48, 95%CI 0.33 to 0.70, p<0.001). Conclusions: In Chinese patients with negative cardiac troponin undergoing DES implantation, indobufen plus clopidogrel DAPT compared with aspirin plus clopidogrel DAPT significantly reduced the risk of 1-year net clinical outcomes, which was mainly driven by a reduction in bleeding events without an increase in ischemic events. [ABSTRACT FROM AUTHOR]

Background: It remains unclear whether indobufen-based dual antiplatelet therapy (DAPT) preserves ischemic protection while limiting bleeding risk in patients with multivessel coronary disease (MVD). This study aimed to investigate the efficacy and safety of indobufen-based DAPT in patients with MVD., Methods: Patients in the OPTION trial were stratified based on the presence of MVD. We compared the ischemic and bleeding risks of indobufen-based DAPT (indobufen 100mg twice a day plus clopidogrel 75mg/d for 12 months) versus conventional DAPT (aspirin 100mg/d plus clopidogrel 75mg/d for 12 months) in patients with and without MVD, using landmarks at 6 months and 1 year post-percutaneous coronary intervention (PCI)., Results: Patients with MVD tended to be older and contained a higher prevalence of high-risk features. Compared with patients without MVD, those with MVD were at higher risk for net adverse clinical events and ischemic events. The risk of ischemic events between indobufen-based DAPT versus conventional DAPT was similar either in patients with MVD or without MVD during the first and second 6 months. During the first 6 months, indobufen-based DAPT decreased the risk of bleeding events consistently in patients with and without MVD. Of note, during the second 6 months, indobufen-based DAPT continually decreased the risk of bleeding events in patients with MVD but not in those without MVD., Conclusions: In patients with MVD, indobufen plus clopidogrel DAPT compared to aspirin plus clopidogrel DAPT could reduce the risk of bleeding events while preserving ischemic protection during both the first and second 6 months post-PCI. Indobufen presents an effective option for patients with MVD, especially those at high ischemic risk requiring DAPT beyond 6 months post-PCI., Trial Registration: The trial was registered at www.chictr.org. A Randomized Controlled Trial of Indobufen versus Aspirin after Coronary Drug-eluting Stent Implantation: the OPTION Trial (ChiCTR-IIR-17013505)., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: This study compared the effect of indobufen with that of aspirin on platelet function in patients with stable coronary heart disease after percutaneous coronary intervention (PCI). Methods: Patients with stable coronary heart disease who had undergone PCI and received dual antiplatelet therapy (aspirin 100 mg + clopidogrel 75 mg once daily) for at least 12 months were allocated to receive indobufen 100 mg twice daily + clopidogrel 75 mg once daily, clopidogrel 75 mg once daily alone, indobufen 100 mg twice daily alone, and aspirin 100 mg once daily alone for 1 month each in an open-label crossover manner. Platelet function was assessed by using the rates of arachidonic acid (AA)-induced platelet aggregation (AA-PAR) and adenosine diphosphate (ADP)-induced platelet aggregation (ADP-PAR) measured by light transmission aggregometry, the platelet reactivity index measured by vasodilator-stimulated phosphoprotein (PRI-VASP), and the plasma and urinary thromboxane B2 (TXB2) concentrations recorded at baseline and during each treatment phase. Results: Of 56 patients enrolled, 52 completed the study. The AA-PAR was lower in the indobufen alone group than in the aspirin alone group [5.21% (3.39, 7.98) vs. 5.27% (4.06, 6.60), p = 0.038], while biologically, a difference of 0.06% may represent no significant difference; there was no significant betweengroup difference in the plasma [531.16 pg/ml (203.89, 1035.06) vs. 373.93 pg/ml (194.04, 681.71), p = 0.251] or urinary [3951.97 pg/ml (2006.95, 6077.01) vs. 3610.48 pg/ml (1664.60, 6247.61), p = 0.717] TXB2 concentration. When the aspirin + clopidogrel group and indobufen + clopidogrel group were compared, similar results were found for AA-PAR [3.97% (3.05, 5.12) vs. 3.83% (3.10, 5.59), p = 0.947] and both plasma [849.47 pg/ml (335.96, 1634.54) vs. 455.41 pg/ml (212.47, 1489.60), p = 0.629], and urinary [4122.97 pg/ml (2044.96, 7459.86) vs. 3812.81 pg/ml (1358.95, 6021.07), p = 0.165] TXB2 concentrations. ADP-PAR was lower in the clopidogrel alone group than in the indobufen alone group (47.04% ± 16.89 vs. 61.7% ± 10.50, p < 0.001), as was PRI-VASP (66.53% ± 18.06 vs. 77.72% ± 19.87, p = 0.002). Conclusion: These findings suggest that indobufen has antiplatelet effects similar to those of aspirin in patients with stable coronary heart disease after PCI, and may be an alternative for patients with aspirin intolerance after coronary stenting. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the pharmacodynamic effects of indobufen and low-dose aspirin in patients with coronary atherosclerosis. Methods: In the first phase, 218 patients with coronary atherosclerosis were randomly assigned to receive aspirin 100 mg once daily (standard dose); 100 mg once every 2 days; 100 mg once every 3 days; 50 mg twice daily; 75 mg once daily; 50 mg once daily; or indobufen 100 mg twice daily for 1 month. In the second phase, 20 healthy subjects were treated with indobufen 100 mg twice daily for 1 week followed after a 2-week washout by aspirin 100 mg once daily for 1 week. The primary outcome was arachidonic acid-induced platelet aggregation (PLAA), and the secondary outcomes included plasma thromboxane B2 (TXB2) and urinary 11-dehydro-TXB2 (11-dh-TXB2) levels at the end of each treatment. Results: In the first phase, compared with aspirin 100 mg once daily: all aspirin groups had similar suppression of PLAA whereas indobufen group had significantly less suppressed PLAA. Aspirin given every second or third day, and indobufen produced less suppression of plasma TXB2. All treatment regimens produced similar inhibition of 11-dh-TXB2. In the second phase, compared with aspirin, indobufen produced less suppression of plasma TXB2 at 8 h and 12 h after the last dose. Conclusions: Aspirin 50 mg twice daily, 75 mg once daily, and aspirin 50 mg once daily produce antiplatelet effects that are similar to aspirin 100 mg once daily. Aspirin given less often than once daily and indobufen 100 mg twice daily do not suppress platelets as effectively as aspirin 100 mg once daily. [ABSTRACT FROM AUTHOR]

Indobufen (Ibustrin®), a reversible inhibitor of platelet aggregation, exists in two enantiomeric forms in 1:1 ratio. Here, we characterized the anti-platelet effect of S- and R-indobufen using response surface modeling using NONMEM® and predicted the therapeutic doses exerting the maximal efficacy of each enantioselective S- and R-indobufen formulation. S- and R-indobufen were added individually or together to 24 plasma samples from drug-naïve healthy subjects, generating 892 samples containing randomly selected concentrations of the drugs of 0-128 mg/L. Collageninduced platelet aggregation in platelet-rich plasma was determined using a Chrono-log Lumi-Aggregometer. Inhibitory sigmoid Imax model adequately described the anti-platelet effect. The S-form was more potent, whereas the R-form showed less inter-individual variation. No significant interaction was observed between the two enantiomers. The anti-platelet effect of multiple treatments with 200 mg indobufen twice daily doses was predicted in the simulation study, and the effect of S- or Rindobufen alone at various doses was predicted to define optimal dosing regimen for each enantiomer. Simulation study predicted that 200 mg twice daily administration of S-indobufen alone will produce more treatment effect than S-and R-mixture formulation. S-indobufen produced treatment effect at lower concentration than R-indobufen. However, inter-individual variation of the pharmacodynamic response was smaller in R-indobufen. The present study suggests the optimal doses of R-and S-enantioselective indobufen formulations in terms of treatment efficacy for patients with thromboembolic problems. The proposed methodology in this study can be applied to the develop novel enantio-selective drugs more efficiently. [ABSTRACT FROM AUTHOR]

Indobufen is a new generation of anti-platelet aggregation drug, but studies were not sufficient on its anticoagulant effects. In the present study, the anticoagulant activity of indobufen was determined by monitoring the activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) in rabbit plasma. We evaluated the anticoagulant mechanisms on the content of the platelet factor 3,4 (PF3,4), and the coagulation factor 1, 2, 5, 8, 10 (FI, II, V, VIII, X) in rabbits, as well as the in vivo bleeding time and clotting time in mice. The pharmacodynamic differences between indobufen and warfarin sodium, rivaroxaban, and dabigatran were further studied on thrombus formation and the content of FII and FX in rats. Animal experiments showed that intragastric-administrated indobufen can significantly reduce the APTT, PT, TT, PF3, FI, II, V, VIII, and X plasma contents. Its inhibitory effect on plasma FII was better than thrombin inhibitor dabigatran with effect on FX better than FXa inhibitor rivaroxaban. These results suggest that indobufen has some anticoagulant effects as strong as some conventional anticoagulants. The mechanism may be related to both exogenous and endogenous coagulation system.

The aim of this study is to quantify the extent and recovery of platelet inhibition after administration of indobufen and aspirin in healthy volunteers. Indobufen inhibits platelet aggregation by reversibly inhibiting the platelet cyclooxygenase enzyme, thereby suppressing thromboxane synthesis. Twenty healthy volunteers completed the study and received aspirin (200 mg/day for 2 weeks) followed by a 4-week washout period and then indobufen (200 mg twice a day for 2 weeks). The percent (%) inhibition of platelet aggregation (IPA) was assessed using arachidonic acid (0.5 mg/ml) and adenosine diphosphate (5 µM) at 4, 12, 24 and 48 hours after last dose of each drug. IPA assessed using arachidonic acid as the agonist was similar at 4 hours after the last dose of indobufen (81.07 ± 9.36%) and aspirin (96.99 ± 0.29%,p = 0.10), but significantly lower at 12 hours (74.04 ± 9.55% vs. 97.94 ± 0.28%,p = 0.02), 24 hours (33.39 ± 11.13% vs. 97.48 ± 0.32%,p < 0.001) and 48 hours (14.12 ± 9.74% vs. 98.22 ± 0.31%,p < 0.001) after indobufen, compared to the relative values for aspirin. IPA assessed using adenosine diphosphate as the agonist was similar in the two groups at 4, 12 and 24 hours after the last dose, but significantly lower 48 hours after the last dose of indobufen, compared to the relative value for aspirin (1.98 ± 3.57% vs. 12.61 ± 2.71%,p = 0.002). Indobufen (200 mg twice a day) caused equivalent initial inhibition of platelet aggregation to aspirin (200 mg daily), and the anti-aggregation effect diminished faster than after aspirin. [ABSTRACT FROM AUTHOR]

Background--The most suitable approach for patients with aspirin hypersensitivity undergoing percutaneous coronary intervention remains to be assessed. Methods and Results-- Pubmed, Google Scholar, and Cochrane were systematically searched for papers describing protocols about aspirin hypersensitivity in the percutaneous coronary intervention setting. Discharge from hospital with aspirin was the primary end point, whereas rates of adverse reactions being a secondary outcome. An online international survey was performed to critically analyze rates of aspirin hypersensitivity and its medical and interventional management. Eleven studies with 283 patients were included. An endovenous desensitization protocol was performed on one of them, with high efficacy rate (98%) and a low adverse reaction rate when compared with oral administration. No significant differences were reported among the oral protocols in terms of efficacy (less versus more fractionated [95.8% {95.4%- 96.2%} versus 95.9% {95.2-96.5%}]), whereas higher incidence of rash and angioedema were reported for protocols with <6 doses escalation (2.6% [1.1%-4.1%] versus 2.6% [1.9%-3.2%]). In the survey, we collected answer from 86 physician of the 100 interviewed. Fifty-six percent of them managed aspirin hypersensitivity changing the therapeutic regimen (eg, clopidogrel monotherapy and indobufen). Despite the previous safety data, desensitization protocols were adopted by only 42% of surveyed cardiologist. Conclusions--Available protocols for aspirin hypersensitivity are effective and safe, representing a feasible approach for patients needing dual antiplatelet therapy. [ABSTRACT FROM AUTHOR]

The prescription of aspirin (acetylsalicylic acid (ASA)) to patients with a history of hypersensitivity to this drug could prove harmful. The aim of the study was to assess the antiplatelet activity and safety of a combined antiplatelet treatment with indobufen and clopidogrel in acute coronary syndrome (ACS) patients with hypersensitivity to aspirin, undergoing coronary stenting. Forty-two consecutive ACS patients treated with stent implantation were randomly assigned to receive clopidogrel 75 mg daily (loading dose 300 mg) plus indobufen 100 mg twice a day (group A), or clopidogrel 75 mg daily, after 300 mg of loading dose (group B). Platelet activity and safety were monitored in both groups at 1, 3, 6, 12, and 18 months with laboratory and clinical evaluation. A lower value of max % platelet aggregation to arachidonic acid and collagen was found in group A compared to group B (31.79 ± 27.33 vs. 73.67 ± 19.92; p < 0.0001 and 28.53 ± 21.32 vs. 73.58 ± 17.71; p < 0.0001, respectively). There was no difference in max % of platelet inhibition to adenosine diphosphate between the two groups (14.23 ± 18.92 vs. 10.30 ± 18.97; p = 0.23). In the population that was under indobufen treatment, the serum thromboxane B2 (TXB2) production at 1 week and 1 month was very low (2.6 ± 1.6 ng/ml and 3.0 ± 2.7 ng/ml, respectively; p = 0.82). The combined treatment was well tolerated in group A patients. This study suggests that the combined antiplatelet treatment with clopidogrel and indobufen could be a good option in ACS patients with hypersensitivity to aspirin undergoing coronary stenting. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To assess whether indobufen, a reversible inhibitor of platelet cyclooxygenase (Cox) activity, affects tissue factor (TF) in human monocytes and to investigate the relationship between Cox-derived products and TF. Methods: TF was evaluated in isolated adherent monocytes, both resting and lipopolysaccharide (LPS)-stimulated, in terms of procoagulant activity, protein, and mRNA levels. The expression of TF surface antigen was determined in LPS-stimulated whole blood monocytes by flow cytometry. The levels of the stable thromboxane A2 (TxA2) metabolite, TxB2, and of prostaglandin E2 (PGE2) were measured in monocyte supernatant by immunoenzymatic techniques. Cox-1 and Cox-2 protein level, tyrosine phosphorylation, and mitogen-activated protein kinase (MAP-kinase) activation were determined by Western blot analysis. Results: Indobufen prevents TF expression and activity both in isolated and in whole blood monocytes. Reduction of TxA2 synthesis, coupled with a lack of effect on PGE2 levels and prevention of ERK1/2 phosphorylation are highlighted as the mechanisms through which indobufen negatively affects TF. Conclusions: Data show that indobufen down-regulates TF in monocytes. This novel activity, coupled with the antiplatelet effect of the drug, may add benefit for its use in the management of atherothrombosis. [Copyright &y& Elsevier]

A direct and stereospecific method was worked out to quantify indobufen enantiomers in human serum using capillary zone electrophoresis (CZE). The indobufen enantiomers and (+)-S-ketoprofen (internal standard, IS) were separated in a fused silica capillary, filled with heptakis 2,3,6-tri-O-methyl-β-cyclodextrin as a chiral selector in a buffer of pH 5.0. Indobufen enantiomers and other non-steroidal anti-inflammatory drugs: flurbiprofen, ketoprofen and (+)-S-naproxen were also separated during one analytical run. UV absorbances of indobufen enantiomers were measured at 282 nm. Influence of temperature on resolution of the enantiomers, and the electrophoretic parameters: electrophoretic (μep) and electroosmotic (μEOF) mobilities were also determined. Validation of the method was carried out. Calibration curves of indobufen enantiomers were linear in the range of 0.2–20.0 μg/ml. Percent recovery of both enantiomers from acidified serum was calculated after extraction with methylene chloride. Intra- and inter-day measurement precision and accuracy were below 15.0%. Limits of quantitation and detection were also estimated. The elaborated method was tested in vivo after administration of a single dose of 200 mg rac-indobufen tablets to healthy volunteers. Calculated parameters confirmed usefulness of the method in human pharmacokinetic studies on indobufen enantiomers. The direct CZE method can provide an alternative to HPLC, where enantiomers used to be derivatised before determination. [Copyright &y& Elsevier]

We have studied the effect of indobufen, a cyclo-oxygenase blocking agent which has proved useful in patients with obstructive vascular disease, on red blood cell (RBC) filterability in vitro and in a pilot study ex vivo. The addition of indobufen in vitro to blood samples from 10 healthy volunteers did not significantly modify RBC deformability. We evaluated the ex vivo effect of indobufen (200 mg bd) in 14 patients with obstructive vascular disease. A significant improvement in RBC deformability was noted on the 5th, 14th, and 28th days of treatment, 2 h after the morning dose. Acetylsalicylic acid given to 6 similar patients had no effect suggesting that the positive haemorheological effect of indobufen is probably not linked to its cyclooxygenase blocking effect. [ABSTRACT FROM AUTHOR]

A high-pressure liquid chromatographic technique was developed which allowed concurrent measurement of acetylsalicylic acid (ASA) and salicylic acid (SA) in plasma. ASA was extensively deacetylated to SA not only in vivo but also in vitro, even in frozen plasma. The in vitro conversion could be prevented by physostigmine. In vivo, ASA was eliminated within few hours, whereas SA was continuously present following daily administration of conventional doses of ASA. A slight modification of a similar method, originally developed for naproxen determination [9], was found appropriate for measurement of the SA derivative diflunisal, of two non-SA antiinflammatory agents, indomethacin and indoprofen, and of a related anti-platelet agent, indobufen. [ABSTRACT FROM AUTHOR]

Six healthy volunteers received single iv and oral doses of 2-[p-(1-oxo-2-isoindolinyl)phenyl] butyric acid 100 mg (indobufen; K 3920), an inhibitor of platelet aggregation. Plasma levels and urinary excretion of the drug were determined by GLC. Collagen-induced platelet aggregation was assessed turbidimetrically at various intervals after administration. The plasma half-life of the drug was 7-8 h and more than 70% of the administered dose was recovered within 48 h in urine, as unchanged drug and as the glucuronide of indobufen. After oral administration of tablets of two different formulations, the drug was completely absorbed, but one formulation showed faster absorption. The maximal inhibitory effect on platelet aggregation was observed 1 to 4 h after iv administration, and it had decreased by 8 h. After tablets, peak effect and the time of the peak were similar, but activity was significantly prolonged, in accordance with the higher plasma levels found at 8 h. The data suggest that the effect of indobufen on platelets is reversible, and that for this drug platelets behave as a compartment that slowly equilibrates with plasma. [ABSTRACT FROM AUTHOR]