Dabigatran Research Articles (Page 1)

Dabigatran etexilate (DAB), a direct thrombin inhibitor, exhibits limited oral bioavailability (6%-7%), mostly attributable to pH-dependent solubility. To address this issue, Eudragit S100 (EU)-coated liposomes were engineered to safeguard DAB-loaded nanocarriers in the stomach and provide targeted release in the intestine, where absorption occurs through several mechanisms. Liposomal vesicles were prepared using the conventional thin film hydration method. The developed formulations were subjected to physicochemical characterization, which included Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), zeta potential analysis, particle size measurement, polydispersity index (PDI) assessment, entrapment efficiency (EE%), and transmission electron microscopy (TEM). The selected formulation, EU@DAB-Lip4, exhibited advantageous properties: minimal particle size (136.9nm), high EE (92.67%), and colloidal stability (zeta potential -17.3mV). In vitro release demonstrated pH-responsive behaviour, with low gastric release (12.8% at 2hr) and enhanced intestinal release (75.5% at pH7.4). Pharmacokinetic studies in rats demonstrated a 5.6-fold and 2.7-fold enhancement in bioavailability for EU@DAB-Lip4 relative to DAB-Lip and DAB suspension, respectively, as indicated by elevated Cmax (2664 vs. 891 and 554ng/ml) and AUC₀-∞ (21 020 vs. 7236 and 3749ng.hr/ml). EU-coated liposomes constitute a viable platform for enhancing DAB bioavailability and therapeutic efficacy.

IntroductionDirect oral anticoagulants (DOACs) have been widely used in patients with thromboembolism. We previously reported that among DOACs, edoxaban (EDX), a factor Xa (FXa)-specific DOAC, most effectively inhibited the growth of syngeneic non-metastatic murine colon cancer cells implanted in mice via the protease-activated receptor 2 (PAR2) pathway. This study aimed to analyze the effects and mechanism of action of DOACs targeting thrombin or FXa on the metastasis of murine melanoma B16 cells implanted in mice.Materials and MethodsB16 cells (106cells in 100 μL) were implanted into the tail vein of 8-week-old female C57BL/6j mice (n = 5 per group), followed by daily oral administration of DOACs targeting thrombin (dabigatran etexilate [DABE], 50 mg/kg body weight [bw]) or FXa (rivaroxaban [RVX], 5 mg/kg bw; EDX, 10 mg/kg bw) for 14 days. The effects on tumor metastasis on day 15 and the inhibitory mechanism of the DOAC with the strongest inhibitory effect were analyzed.ResultsLung metastasis of B16 cells implanted in mice was significantly suppressed in the following order: EDX > RVX ≥ DABE, compared with the saline-treated group. DOPA (3,4-dihydroxyphenylalanine)-positive cell density was significantly reduced from approximately 1,250 cells/mm2in the saline group to approximately 600 cells/mm2(RVX and DABE) and approximately 400 cells/mm2(EDX;p < 0.05 or 0.01). Investigating the inhibitory mechanism of EDX revealed that inflammation-associated factors such as PAR2, interleukin 6 (IL-6), and transforming growth factor β1 (TGFβ1); angiogenic factors such as vascular endothelial growth factor A and angiopoietin-2; and epithelial–mesenchymal transition (EMT)-associated factors such as vimentin and snail, which were increased in the lungs of the saline-treated group, all significantly decreased in the EDX-treated group (p < 0.05 or 0.01). In contrast, intercellular tight junction factors exhibited an opposite trend. EDX also inhibited FXa-dependent production of melanin, IL-6, and TGFβ1 in in vitro cultured B16 cells.ConclusionAmong the tested DOACs, EDX showed the strongest inhibition of B16 cell metastasis in mice, likely via the suppression of inflammation, angiogenesis, and EMT mediated by the FXa-dependent PAR2 and TGFβ pathways in tumor and surrounding tissue cells.

ABSTRACTBackground:The use of new oral anticoagulants (NOACs) is becoming increasingly widespread, but data on their adverse reactions are still incomplete. Further analysis based on data from the Drug Adverse Reaction Center is needed to guide safe clinical use.Methods:A retrospective analysis was performed on 281 cases of rivaroxaban and 48 cases of dabigatran etexilate-related ADR reported by medical institutions collected by a provincial Food and Drug Administration from 2018 to 2023.Results:Of the 329 ADRs, 164 males and 165 females were reported. Among the rivaroxaban-related ADRs, 271 were administered orally, 6 were given nasogastric feeding, 2 were given tube feeding, and 2 were intravenously instilled. Among the ADRs associated with dabigatran etexilate, 48 cases were administered orally. Serious adverse drug reactions were reported in 21.6% of cases (71 out of 330). The clinical manifestations of ADR of NOACs mainly include blood in the stool, blood in the urine, bleeding gums, coagulation disorders and ecchymosis. The causal relationship between serious adverse reactions and drugs was judged to be very likely in 24, 43 cases was judged to be probable, and 4 cases were unknown.Conclusions:Attention should be paid to the clinical use of NOACs in elderly patients, and pharmacovigilance should be strengthened, and the implementation of individualised medication regimen should be used to promote clinical safety and rational drug use.

Background/Objective: Physiologically based pharmacokinetic (PBPK) modeling is a powerful tool for predicting pharmacokinetics (PK) to support drug development and precision medicine. However, it has not been established for non-renal clearance pathways in patients with end-stage renal disease (ESRD), a population that bears heavy medication burden and is thereby at high risk for drug-drug-disease interactions (DDDIs). Furthermore, the pronounced inter-individual variability in PK observed in ESRD patients highlights the urgent need for individualized PBPK models. Methods: In this study, we developed a PBPK population model for ESRD patients, incorporating functional changes in key drug-metabolizing enzymes and transporters (DMETs), including CYP3A4, OATP1B1/3, P-gp, and BCRP. The model was initially constructed using the recalibrated demographic and physiological parameters of ESRD patients. Then, we used five well-validated substrates (midazolam, dabigatran etexilate, pitavastatin, rosuvastatin, and atorvastatin) and their corresponding PK profiles from ESRD patients taking a microdose cocktail regimen to simultaneously estimate the abundance of all these DMETs. Lastly, machine learning was employed to identify potential factors influencing individual clearance. Results: Our study suggested a significant reduction in hepatic OATP1B1/3 (75%) and intestinal P-gp abundance (34%) in ESRD patients. Ileum BCRP abundance was estimated to increase by 100%, while change in hepatic CYP3A4 abundance is minimal. Notably, simulations of drug combinations revealed potential DDDI risks that were not observed in healthy volunteers. Machine learning further identified Clostridium XVIII and Escherichia genus abundances as significant factors influencing dabigatran clearance. For rosuvastatin, aspartate aminotransferase, total bilirubin, Bacteroides, and Megamonas genus abundances were key influencers. No significant factors were identified for midazolam, pitavastatin, or atorvastatin. Conclusions: Our study proposes a feasible strategy for individualized PK prediction by integrating PBPK modeling with machine learning to support the development and precise use of the aforementioned DMET substrates in ESRD patients.

To evaluate the effects of vepdegestrant, a PROteolysis TArgeting Chimera (PROTAC) oestrogen receptor degrader, on the pharmacokinetics of dabigatran (a P-glycoprotein [P-gp] substrate) and rosuvastatin (a breast cancer resistance protein [BCRP] substrate). In two phase 1, open-label, two-period, fixed-sequence studies, healthy adult participants received a single oral dose of dabigatran etexilate 75 mg or rosuvastatin 10mg alone and with a single dose of vepdegestrant 200 mg. Serial plasma samples were collected after dosing, and pharmacokinetic parameters for dabigatran and rosuvastatin were estimated by standard noncompartmental analysis. Coadministration of the P-gp substrate dabigatran etexilate with vepdegestrant increased dabigatran area under the concentration-time curve (AUC) from time 0 to infinity by 98% and maximum plasma concentration (Cmax) by 92%. Coadministration of the BCRP substrate rosuvastatin with vepdegestrant increased rosuvastatin plasma AUC from time 0 to time of the last measurable concentration by 11% and Cmax by 21%. Coadministration with vepdegestrant doubled dabigatran exposure and resulted in a minor increase (11%) in rosuvastatin exposure in humans.

The ARCADIA-MRI study, an ancillary study to the randomized Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) trial, reported that the risk of incident non-lacunar covert infarcts was lower in the apixaban group than the aspirin group. This paper presents the additional, prespecified, exploratory outcomes beyond the primary paper, specifically examining the effect of apixaban on hemorrhagic lesions on MRI. The ARCADIA-MRI study was conducted in conjunction with ARCADIA trial visits, with follow-up durations ranging from 4 months to 5.3 years (median 27 months). It included randomized patients who were eligible for cognitive testing and lacked MRI contraindications. Two experienced raters, blinded to treatment assignments, independently evaluated the baseline and follow-up MRI scans. The radiological endpoints of this analysis were incident intracerebral hemorrhages (>10 mm), microbleeds (≤10 mm), and superficial siderosis. MRI outcomes were compared between the 79 patients in the apixaban group and 95 in the aspirin group with both baseline and follow-up MRIs available. The treatment groups had similar baseline MRI findings. On the follow-up MRIs, the findings of incident bleeding events were all similar between the treatment groups (all p > 0.05): intracerebral hemorrhages occurred in 5.1% of patients in the apixaban group compared to 6.4% of patients in the aspirin group; microbleeds, 7.8% in the apixaban group and 10.8% in the aspirin group; and cortical superficial siderosis, in 7.7% of apixaban group and 12.9% in the aspirin group. In an exploratory analysis of the ARCADIA-MRI substudy, MRI findings of incident bleeding events were similar in patients randomized to receive apixaban and aspirin. ARCADIA= atrial cardiopathy and antithrombotic drugs in prevention after cryptogenic stroke; AF= atrial fibrillation; DOAC= direct-acting oral anticoagulants; ICH =intracerebral hemorrhage; NT-proBNP= N-terminal pro-B-type natriuretic peptide; NAVIGATE ESUS=Rivaroxaban versus aspirin for prevention of covert brain infarcts in patients with embolic stroke of undetermined source; RE-SPECT ESUS=Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate versus Acetylsalicylic Acid in Patients with Embolic Stroke of Undetermined Source; COMPASS =Cardiovascular Outcomes for People Using Anticoagulation Strategies; ATTICUS study =The Apixaban for Treatment of Embolic Stroke of Undetermined Source.

The bleeding risk associated with dabigatran etexilate (DABE) dosing remains unclear in patients undergoing catheter ablation for atrial fibrillation (AF) because these patients were excluded from the pivotal clinical trial of DABE. This study aimed to evaluate the bleeding risk factors in patients undergoing catheter ablation for AF with anticoagulant therapy using DABE. A retrospective cohort study included 343 patients who underwent catheter ablation with minimally interrupted DABE dosing (n = 167), where only the morning dose was withheld, or with uninterrupted dosing (n = 176), in adherence to the recommended dose reduction criteria. Bleeding events were assessed for 2 d following catheter ablation. Multivariable logistic regression analysis was performed to identify the bleeding risk factors. Bleeding events were observed in 45 (13.1%) patients. Multivariable analysis revealed that concomitant P-glycoprotein inhibitor use was significantly associated with bleeding events (odds ratio, 2.77; 95% confidence interval, 1.40-5.51; p = 0.004), after adjusting for moderate renal impairment. Among patients with uninterrupted DABE dosing, bleeding events occurred more frequently in concomitant users of P-glycoprotein inhibitors than in non-users (32.4 vs. 9.8%, p = 0.002). However, no significant difference was found among those with minimally interrupted dosing (18.2 vs. 10.4%, p = 0.24). Concomitant P-glycoprotein inhibitor use is a significant bleeding risk factor in patients undergoing catheter ablation with DABE. The increased bleeding risk associated with concomitant P-glycoprotein inhibitor use is more pronounced in patients with uninterrupted DABE dosing. Uninterrupted DABE dosing should be employed cautiously in patients using P-glycoprotein inhibitors.

Accurate prediction of oral drug absorption in humans is essential for early drug development; however, physiologically relevant human models are lacking. This study aims to comprehensively assess the EpiIntestinal™, a human primary intestinal 3D model, for its ability to predict oral absorption (Fa), intestinal availability (Fg), CYP3A4 induction, and drug–drug interactions (DDIs). The model showed clinically relevant expression of a key drug‐metabolizing enzymes, transporters, and a nuclear receptor, pregnane X receptor (PXR). The model demonstrated a moderate improvement over Caco‐2 in correlating permeability coefficients with human absorption data for a set of 18 drugs. However, PBPK modeling, using EpiIntestinal™ permeability data, accurately predicted the clinical maximum plasma concentration (Cmax) of the P‐gp substrates digoxin and dabigatran etexilate, unlike the significant underpredictions from Caco‐2 data. PBPK modeling using intrinsic clearance and permeability data from EpiIntestinal™ accurately predicted human Fg for CYP3A4/5 substrate drugs (except buspirone). Furthermore, the model demonstrated the induction of CYP3A4 and P‐gp (threefold) by a strong PXR inducer, rifampicin. Combining induction parameters of rifampicin from EpiIntestinal™ with those from the TruVivo (human hepatic model) into PBPK modeling accurately captured DDI effects on midazolam, a sensitive CYP3A4/5 substrate. Additionally, the model accurately predicted clinical outcomes of P‐glycoprotein (P‐gp) and breast cancer resistance protein (BCRP) mediated DDIs for ARV‐471. These data underscore the potential of EpiIntestinal™ in predicting human Fa and Fg, and in quantitatively assessing CYP3A4 induction and transporter‐based DDIs.

Aim. To evaluate the characteristics of anticoagulant therapy (ACT) use in patients with cardioembolic (CE) subtype ischemic stroke (IS) and atrial fibrillation (AF) hospitalized in a specialized vascular center.Material and methods. A cross-sectional study was conducted at the Vascular Center of Botkin City Clinical Hospital from April 2022 to April 2023. Adults (≥18 years) with confirmed CE-subtype IS and documented AF, presenting within 12 hours of symptom onset and receiving anticoagulants for over one month prior to admission, were eligible. Patients with hemorrhagic stroke or non-CE IS subtypes, those lacking data on anticoagulant use, or those who declined to participate were excluded.Results. Among 1.038 patients with IS, 215 (20.7%) were diagnosed with the CE subtype in the setting of AF. More than half (n=109) were not receiving ACT at the time of stroke onset. A total of 106 patients who had been on outpatient ACT were included; rivaroxaban (n=56), apixaban (n=30), dabigatran etexilate (n=11), and warfarin (n=9). The mean patient age was 77.8 years, with an average CHA2DS2-VASc score of 6. In 33.9% of patients, the prescribed doses of direct oral anticoagulant (DOAC) did not correspond to clinical guidelines (e.g., unjustified dose reductions of rivaroxaban and apixaban were identified). The median National Institutes of Health Stroke Scale (NIHSS) score at admission was 7, and in-hospital mortality reached 30.2%. Elevated mortality was associated with severe stroke presentation (NIHSS score &gt; 8 in half of the patients) and a high burden of comorbidities: hypertension in 95.2%, chronic heart failure in 60.4%, type 2 diabetes mellitus in 30.1%, and prior myocardial infarction in 37.7% of patients.Conclusion. The high incidence of IS despite ongoing anticoagulation highlights the need for routine monitoring of DOAC plasma levels, regular assessment of treatment adherence, and systematic education of patients and their families regarding the importance of strict adherence to prescribed anticoagulant regimens.

ABSTRACT: Our research indicates that chromogen method has beendeveloped fordabigatran, however, for plasma analysis we incorporated a chromogenic approach specifically for dabigatran in plasma. To ensure a simple and accurate assessment, a spectrophotometric technique has to be developed and validated for for the quantiifcation ofdabigatran etexilate mesylate (DAB) in bulk and pharmaceutical dose forms. This method uses the 1-Naphthol reagent, which yields a colored complex facilitating precise measurement.To develop a novel, straightforward, accurate, repeatable, and exact chromogenic UV-visible spectroscopy, and bioanalytical technique, for measuring dabigatran etexilate mesylate in pharmaceutical formulations and bulk. In the presence of Sodium Nitrite and HCl with Ammonium Sulfamate, amine undergoes diazotization. DAB and 1-Naphthol react to generate a green complex that can be detected at 449 nm. Chromogenic method was used for quantification of dabigatran in incurred plasma and quality control samples. Method development and validation for quantification of dabigatran was developed and validated.Human serum UV-visible spectroscopy was created and verified. Plasma was extracted with protein precipitation by acetonitrile. Recoveries for both incurred plasma and quality control sample exceeded 89.48% while accuracy fell below 101.26% and 101.96% respectively and RSD less than 10% each. Overall, we conclude that the method developed was sensitive and accurate for easy analysis of plasma incorporated with chromophore/reagent. The findings of results are more accurate data and validated as per proceeded guidelines i.e, M10.

A well-founded choice of means of medical support for patients after total hip arthroplasty and rational use of financial resources for this purpose allow to achieve the maximum possible socio-economic effect in the future. Its methodological basis is made up of clinical and economic concepts based on the concepts of cost (price, expenses) and clinical effectiveness of the intervention (treatment results). The aim of the study was to determine the financial component of medical support in the postoperative period of total hip arthroplasty using ABC/VEN analysis (Vital Essential Non-essential). In the current study, the ranking of medical products when conducting both ABC/VEN analysis was carried out by the number of prescriptions. The number of prescriptions is a more indicative approach, as it demonstrates the real frequency of drug use in practice, the relevance and demand for specific medications in real-world conditions, allowing for a more accurate determination of priority drugs for clinical use and, accordingly, providing a more relevant and practical assessment of drug needs. The number of observations (n), minimum and maximum values (min – max) were used to describe the variables, quantitative data were presented as the arithmetic mean and standard deviation. Qualitative data - in the format n (%). Results - analysis of prescriptions from medical records of patients with dysplastic coxarthrosis revealed that 6548 prescriptions were made for 367 people during the study period. The results of the integrated ABC/VEN analysis showed that in the context of the most costly group “A”, the main financial resources were spent on providing long-term antithrombotic therapy to prevent pulmonary embolism and lower limb vein thrombosis, the total amount for 2754 prescriptions (42.1% of all prescriptions) was 1,745,478.90 UAH. Less costly (group “B”, 2351 prescriptions) were drugs prescribed for antibiotic prophylaxis of infectious complications. In general, the costs of drugs in group “B” (35.9% of all prescriptions) amounted to 552,820.30 UAH, which corresponded to 21.6% of the financial costs for medical support of patients after TEP. The least expensive group "C" consisted mostly of secondary category N means, which accounted for 17.9% (1173 out of 6548) of the total number of prescriptions and accounted for 6.7% (171,986.75 out of 2,559,353.23 UAH) of the total amount of expenses. «Vital» category V means in this analysis group accounted for 4.1% (270 out of 6548) of all prescriptions, and the expenses for them were 3.5% (89,067.28 out of 2,559,353.23 UAH). The share of financial expenses for these means amounted to half (52.8%) of the total budget for medical support of patients after total hip arthroplasty, which in monetary equivalent was 1,350,380.53 UAH. The leading positions in terms of costs were occupied by vital category V drugs – the synthetic selective inhibitor of activated factor X fondaparinux (“Arixtra”) and the competitive reversible direct thrombin inhibitor dabigatran etexilate (“Pradaxa”), the share of prescriptions of which was 89.4% and 82.3%, respectively.

Identifying oral and parenteral drugs associated with esophageal ulcers is important. A comprehensive analysis of a spontaneous adverse event reporting database can support early detection and prevention of drug-induced esophageal ulcers. Drug-induced esophageal ulcers are primarily associated with orally administered drugs. However, recent studies have suggested potential association with parenterally administered drugs. These parenteral cases have not been comprehensively analyzed in previous research. We conducted disproportionality analysis using data from the Japanese Adverse Drug Event Report (JADER) database between April 2004 and December 2023. Signals for esophageal ulcers were detected using the reporting odds ratio with a 95% confidence interval. Weibull distribution analysis was performed to determine the time to adverse event onset for drugs showing signals of esophageal ulcers. Orally and parenterally administered drugs were analyzed separately. Signals were detected for 15 orally administered drugs and 7 parenterally administered anticancer drugs. Weibull distribution analysis revealed that doxycycline and dabigatran etexilate induced the early onset of pill-induced esophagitis, with median onset times of 8 and 12.5 days. Meanwhile, bevacizumab and paclitaxel showed consistent occurrence patterns of esophageal ulcers throughout the treatment period. Our comprehensive analysis of the JADER database identified signals for esophageal ulcers associated with both oral and parenteral drugs, along with their characteristic onset patterns. These findings highlight the clinical importance of considering the potential for esophageal ulcers with specific oral and parenteral drugs and suggest that early intervention may be crucial in mitigating their occurrence.

In clinical practice, it is sometimes necessary to administer the thrombin inhibitor dabigatran etexilate (DE) to patients who have difficulty taking medications by mouth, but little is known about the pharmacokinetics and plasma concentrations of DE when it is administered via gavage. We describe a case in which it was necessary to orally administer the decapsulated contents of DE capsules. A 79-year-old man with atrial fibrillation, quadriplegia, and a history of liver dysfunction who had difficulty swallowing was administered DE via a nasogastric tube while monitoring his plasma dabigatran concentration. To prepare the DE for administration, the contents of DE capsules were suspended in water. Despite administering only half the standard dose, the patient's blood dabigatran concentrations were comparable to those of patients receiving a full dose, potentially due to improved solubility and dispersion in the gastrointestinal tract after decapsulation. Coagulation status, as measured by activated partial thromboplastin time (aPTT), remained within safe limits, with no significant bleeding. DE was administered via a nasogastric tube for 8 days with monitoring. This case suggests that, for patients who cannot take medication orally, DE can be administered safely via a nasogastric tube at lower doses while closely monitoring blood drug concentrations and aPTT levels. Further research is needed to explore the pharmacokinetics and understand the impact of diet on the absorption of DE administered via nasogastric tube. This administration method may broaden treatment options for atrial fibrillation in patients with difficulty in oral intake.

e15127 Background: Debio 0123 is an oral, brain-penetrant, highly selective WEE1 kinase inhibitor currently being investigated in several clinical trials in patients with advanced solid tumors both as monotherapy and in combination. In vitro , Debio 0123 can inhibit and induce cytochrome P450 (CYP) 3A4 and inhibit P-gp. Methods: A physiologically-based pharmacokinetic (PBPK) model using Simcyp Population Based Simulator was developed for Debio 0123 to evaluate its perpetrator effect on sensitive substrates of CYP3A4 and P-gp. A second model was developed for etoposide as victim drug. Both were combined to assess the risk of clinical drug-drug interaction (DDI) between Debio 0123 and etoposide. Plasma etoposide concentrations were simulated following single and three daily doses of etoposide 100 mg/m 2 IV administered concomitantly with, or without, 520 mg oral (PO) Debio 0123. The Debio 0123 model was developed using in vitro and clinical data from previous Debio 0123 clinical trials. Results: No clinically significant DDIs were predicted between Debio 0123 given for 3 consecutive days and the CYP3A4 probe substrate, midazolam. When PO or IV administration of midazolam was simulated, the 90%CI of the geometric mean ratio (GMR) for AUC inf and C max , alone versus in combination with Debio 0123, entirely fell within 0.9 and 1.3. A weak DDI was predicted towards the P-gp probe substrate dabigatran etexilate. When given orally, AUC inf and C max GMR of dabigatran with, or without, Debio 0123 were 1.87 and 1.93, respectively. Administration, for 3 consecutive days, of Debio 0123 combined with IV etoposide was predicted to have no effect on etoposide exposure (90%CI of GMR for both AUC and C max within 0.80-1.25). Accordingly, the design of Debio 0123-SCLC-104 trial with Debio 0123 administered in combination with carboplatin and etoposide (NCT05815160 - ASCO 2025 # 495064) was developed with standard doses of IV etoposide. To confirm the absence of DDI, PK samples were collected in the trial. No major changes were noted in the observed etoposide exposure across Debio 0123 dose levels (200 to 400 mg) after one or three days of co-administration in adult SCLC participants that recurred or progressed after previous platinum treatment. Etoposide PK observed in the study was also in line with literature data (US label Etopophos 2011). Debio 0123 PK was consistent with data previously reported for monotherapy (Abstract #3120 ASCO 2024). Conclusions: Overall, these results indicate that there is no relevant PK interaction between Debio 0123 and IV etoposide. For concomitant medications that are P-gp substrates, only a weak DDI is expected with Debio 0123. Furthermore, the absence of significant DDIs predicted with CYP3A4 substrates suggests that Debio 0123 can be combined with a wide range of therapies. Clinical trial information: NCT05815160 .

There was a lack of bibliometric analyses of postoperative deep vein thrombosis (DVT) after total hip arthroplasty (THA), and this study aimed to provide a comprehensive overview of the knowledge structure and research hotspots in this area through visual analyses. The Web of science (WOS) core databases were searched for relevant studies built up to March 2024, and CiteSpace was then used to create a network diagram, analyze the authors, institutions, nations, journals, keywords, and references in this field generally, as well as to investigate hotspots and trends in research in this field. There were 1,299 pertinent papers in all, and the number of publications in the topic was generally rising. The author with the highest number of publications is Parvizi, Javad, and the institution is Jefferson University, while the United States is the most influential and contributing country in the field, the top 5 high frequency keywords are venous thromboembolism, deep vein thrombosis, prevention, total hip arthroplasty, replacement; the keyword dabigatran etexilate has the highest burst intensity in burst detection, while aspirin, blood management, and risk stratification are emerging research trends. This study examines the literature on postoperative DVT following THA using CiteSpace, which offers useful data for possible cooperation between authors, countries, and research institutions. It also identifies hotspots and trends for future research, which will be a resource for scholars looking to delve deeper into the preventive measures for DVT following THA.

Background: Diabetes mellitus type-1 is an immunological disease associated with low insulin release and hyperglycemia due to beta cell loss. No clear studies show the relationship between the coagulation cascade activation and diabetes mellitus type-1 development. Objective: The present work aimed to clarify the function of the active coagulation system in the progression of diabetes mellitus type-1 (T1DM). Furthermore, the possible protective action of direct thrombin inhibitors (dabigatran) against T1DM caused by streptozotocin (STZ)-induced T1DM in mice model was examined. Materials and Methods: Forty Balb/c male albino mice were distributed into four different groups, with 10 mice in each group: normal, dabigatran (DAB)-treated, STZtreated, and STZ+DAB. Blood glucose, blood platelets, serum insulin, nuclear consistency, and pancreas histopathological changes were evaluated. Moreover, the expressions of PI3K, p-Akt, insulin, and fibrinogen were investigated in the pancreatic tissues via immunofluorescent technique. Results: The findings displayed enhanced islet expression of fibrinogen, p-Akt, and PI3K proteins along with thrombocytopenia in STZ-injected mice when equated to control. Furthermore, treatment with STZ reduced pancreatic insulin expression. DAB and STZ-cotreatment significantly diminished pancreatic tissue expression of fibrinogen, PI3K, and p-AKT, as well as increased platelet counts and pancreatic insulin expression. Conclusion: The evidence supported the activation of coagulation cascade in T1DM through the PI3K/AKT pathway. Using direct antithrombin therapy may open new avenues for T1DM prevention in high-risk diabetes individuals.

Comparison of Dabigatran Etexilate Self-Micro-Emulsifying Drug Delivery Systems Formulation Optimization Techniques: Design Expert Vs. MATLAB

Design, synthesis and anticoagulant activity evaluation of deuterium-labeled dabigatran etexilate and its intermediate derivatives

Polymorphic Stability and Enhanced Drug Release of Dabigatran Etexilate Mesylate in Mesoporous Silica-Based Liquisolid Systems- Formulation and In Vitro Evaluation

Gastric stress events impact the bioavailability of a poorly soluble weak base dabigatran from pellet-filled capsules: An outcome from pharmacokinetic simulations based on biorelevant dissolution testing, machine learning, and a novel timewise first-order dissolution model.