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Objective To explore the efficacy and safety of dabigatran etexilate in the treatment of elderly patients with non-valvular atrial fibrillation (NVAF), so as to provide reference for clinical treatment and rational drug use. Methods Eighty elderly patients with NVAF in The Seventh People's Hospital of Shanghai from December 2020 to June 2021, aged 65 to 80 years, were enrolled in a self-controlled study. Dabigatran etexilate 110 mg was given orally, twice a day (one in the morning and one in the evening) for 6 months. During the follow-up visit, the coagulation function indexes including APTT, TT, FIB and D-D were observed in patients taking medicine for 1 month and 6 months. Liver function indexes including ALT, AST and TBIL, renal function indicators including UREA and eGFR, and blood routine indexes including HGB and ESR, also were observed in patients taking medicine for 1 month and 6 months. Results Patients were compared at 1 month and 6 months after treatment with dabigatran and before: the difference of coagulation function indexes as APTT and TT was statistically significant (P<0.05);There was no significant difference in liver function index, renal function index and blood routine index (P>0.05); A total of 25 adverse events occurred, and the incidence rate of adverse reactions was 31.25%, there was no adverse events such as serious hemorrhage，life threatening and organ failure hemorrhage occurred．Conclusion Dabigatran has good efficacy and safety in the treatment of the elderly NVAF.
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@#Dabigatran etexilate mesylate(DE)and tadalafil(TD)are BCS class II drugs with poor water solubility. 〓 In this study coamorphization technique was used to improve their solubilities/dissolutions and hence to enhance their oral absorptions. The coamorphous DE-TD were prepared by solvent-evaporation method and characterized by PXRD, DSC, FTIR and TGA. In addition, dissolution behavior and physical stability were also investigated. Only halo pattern and a single Tg of 119 °C was observed on the PXRD and DSC of the co-evaporated product, respectively, indicating the formation of coamorphous DE-TD. FTIR result suggested that a hydrogen bond was probably formed between N-H group of DE and C==O group of TD. In comparison to crystalline counterparts, coamorphous DE-TD showed a significantly improved intrinsic dissolution rate and prolonged supersaturation time in intrinsic dissolution and supersaturation dissolution studies, respectively. No crystallization was observed under affecting factors testing(30 days)as well as long-term and accelerated stability testing(90 days)for the prepared coamorphous DE-TD under 25°C/60%RH or 40°C/75%RH, while amorphous DE crystalized at 10 days under 25 ℃/75% RH.
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Objective To observe the effect of low-dose dabigatran etexilate on the clinical efficacy of elderly patients with venous thromboembolism (VTE). Methods Seventy-five elderly (≥ 80 years old) VTE patients admitted to Cangzhou Central Hospital from October 2016 to June 2018 were enrolled, they were treated according to the VTE guidelines, and low dose dabigatran etexilate was the anticoagulant therapy selected, 110 mg once daily for 6 months. After treatment for 6 months, the thrombus regression situation with color Doppler ultrasonography;clinical efficacy was evaluated by clinical symptoms and ultrasonographic results, the changes in platelet count (PLT), coagulation parameters [international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (Fib)] before and after treatment were detected and the occurrence of adverse reactions were recorded and safety of drug was evaluated. Results There were no significant differences in PLT, INR and Fib before and after treatment [PLT (×109/L): 197.88±58.00 vs. 199.88±65.15, INR: 1.02±0.10 vs. 1.05±0.13, Fib (g/L): 2.89±0.67 vs. 2.84±0.70, all P > 0.05], the APTT after treatment was significantly prolonged compared with that before treatment (seconds:40.9±7.34 vs. 26.2±3.16), the difference being statistically significant (P < 0.05), the amount of APTT prolongation after treatment did not exceed 2 times [average (1.75±0.24) times] of the baseline value before treatment. The total effective rate of low-dose dabigatran etexilate for treatment of elderly patients with VTE for 6 months was 90.7% (68/75);no obvious adverse reactions occurred during the treatment. Conclusion Low-dose dabigatran etexilate for treatment of elderly patients with VTE is safe and effective without any obvious adverse reactions, and is worthy to be promoted for clinical use.
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OBJECTIVE:To compare anticoagulant efficacy and safety of dabigatran etexilate and warfarin in the treatment of non-valvular atrial fibrillation(NVAF). METHODS:In retrospective analysis,360 NVAF patients were divided into control group (180 cases)and observation group(180 cases)according to therapy plan. Control group was given Warfarin sodium tablet with ini-tial dose of 2.5 mg orally,once a day,adjusted dosage according to INR. Observation group was given Dabigatran etexilate cap-sule 150 mg with warm water,twice a day,during or after meal. The levels of ALT,AST and INR,the occurrence of ADR were observed in 2 groups before treatment and 1,3 month after treatment. RESULTS:There was no statistical significance in the levels of ALT or AST between 2 groups before and after treatment (P>0.05). Before treatment,there was no statistical significance in INR between 2 groups (P>0.05),1,3 months after treatment,INR in control group was significantly higher than before treat-ment,with statistical significance(P<0.05);there was no statistical significance in the INR of observation group before and after treatment(P>0.05);but INR of 2 groups ranged were in normal range. There was no statistical significance in the incidence of ADR between 2 groups(P>0.05). CONCLUSIONS:Anticoagnlant efficacy of dabigatran etexilate is significantly better than war-farin for NVAF. Both have similar safety.
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In order to research the related substances of dabigatran etexilate mesylate,seven related compounds were synthesized and the related detection methods were established (Using XBridge C18 as the column,methanol-0.01mol/L potassium dihydrogen phosphate as the mobile phase Gradient elution,detection wavelength of 310 nm).The solvents and the injection volume were also screened.Results showed that the established method could separate the dabigatran etexilate mesylate and seven compounds completely,and the reproducibility was good and the accuracy was high,which was suitable for the detection of the related substances of dabigatran etexilate mesylate.
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OBJECTIVE: To determine two toxic impurities, namely bromoacetic acid and 4-aminobenzonitrile, in the intermediate of dabigatran etexilate by UHPLC-MS. METHODS: The separation was performed on a Shimadzu Shim-Pack GIS C18 column (2.1 mm×50 mm, 2 μm) with mobile phase consisting of 0.1% formic acid aqueous solution (A) and 0.1% formic acid methanol (B) by gradient elution at a flow rate of 0.4 mL·min-1. The detection was achieved by triple quadrupole mass spectrometry with rapid polarity switching using MRM mode. RESULTS: The calibration curves were linear in the ranges of 0.2-40 and 0.4-40 ng·mL-1 for bromoacetic acid and 4-aminobenzonitrile, respectively. The values of LOQ of bromoacetic acid and 4-aminobenzonitrile were 0.1 and 0.4 ng·mL-1, respectively. The recoveries of bromoacetic acid and 4-aminobenzonitrile were 100.9% and 99.6%, respectively. CONCLUSION: The method is accurate, rapid, sensitive, and reliable to determine the two toxic impurities bromoacetic acid and 4-aminobenzonitrile in the intermediate of dabigatran etexilate for quality control.
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@#The purpose of this study was to prepare dabigatran etexilate nanoemulsion to improve bioavailability of dabigatran etexilate, a poorly water-soluble drug. The physicochemical properties and the stability of dabigatran etexilate nanoemulsion were investigated. Equilibrium solubility of dabigatran etexilate in commonly used oil materials for nanoemulsion were determined for selection. Then, surfactant and co-surfactant were chosen based upon the plooted pseudo-ternary diagrams. The formulation and preparation process were further optimized with orthogonal design. As a result, the dabigatran etexilate nanoemulsion was formulated based on the system consisting of Oil Acid/Labrafac Lipophile WL1394/Cremophor RH40/Transcutol P/H2O. The dabigatran etexilate nanoemulsion was found to have a mean diameter of(57. 5±0. 2)nm, Zeta potential of -(20. 9±1. 4)mV, and the drug encapsulation efficiency of(85. 2±1. 0)%. Besides, the droplet size, stability constant and drug content of the nanoemulsion was found to have no significant changes in at least 3 months under room temperature. In conclusion, the uniform and stable dabigatran etexilate nanoemulsion with a clear and translucent appearance was obtained after the optimization of formulation and preparation process. Thus nanoemulsion could be a promising way for the improvement of bioavailability of dabigatran etexilate and other poorly water-soluble drugs.
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OBJECTIVE:To explore the effect of dabigatran etexilate on coagulation indexes and safety of elderly patients with persistent atrial fibrillation. METHODS:52 elderly patients with persistent atrial fibrillation were randomly divided into obser-vation group and control group by random number table,26 cases in each group. Creatinine clearance rate in observation group was higher than 30 ml/min,110 mg Dabigatran etexilate capsule was orally given,bid;when 15-30 ml/min,55 mg capsule was orally given,bid. Control group orally received Warfarin sodium tablet with initial dose of 2.5 mg,qd,according to international normal-ized ratio (INR) after 3-5 days till maintained in 2.0-3.0. After 3 months,coagulation indexes [prothrombin time (PT),activated partial thromboplastin time (APTT),thrombin time (TT),INR,platelet count (PLT),fibrinogen (FIB)] before and after treat-ment,incidences of clinical events (cerebral embolism,cerebral hemorrhage,fatal bleeding,the remaining parts of embolism, death)and adverse reactions in 2 groups were compared. RESULTS:There was no significant difference in PT,APTT,TT,PLT and FIB between 2 groups before treatment(P>0.05);after treatment,PT and INR in 2 groups significantly increased,and obser-vation group was obviously better than control group,the difference was statistically significant(P0.05);the incidence of remaining parts of embolism,death in observation group significantly lower than control group,the difference was statistically significant(P<0.05). The incidence of adverse reactions in observation group was significant-ly lower than control group,the difference was statistically significant (P<0.05). CONCLUSIONS:Dabigatran etexilate shows good coagulation effect on elderly patients with persistent atrial fibrillation,which can effectively improve PT and INR levels and reduce the incidences of clinical events,with good safety.
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Dabigatran etexilate is one of the new oral anticoagulants approved to reduce the risk of stroke in patients with atrial fibrillation (AF). A variety of bleeding complications with dabigatran have been reported, but reports of hemopericardium are rare. We described a case of a 66 year-old female patient with non-valvular AF receiving dabigatran etexilate 150 mg twice daily for one year who suffered from hemopericardium. Her laboratory tests performed 1 year prior were normal and her admission tests revealed acute renal failure and elevated international normalized ratio (INR) level (4.79). Urgent pericardiocentesis was followed by improved renal functions and normalized INR. Dabigatran etexilate is a new oral anticoagulant that is increasingly used in daily practice. However, life-threatening complications warrant caution. Elevated INR may be related with overdose but the association of bleeding risk of dabigatran and INR requires further confirmation.
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Female , Humans , Acute Kidney Injury , Anticoagulants , Atrial Fibrillation , Cardiac Tamponade , Hemorrhage , International Normalized Ratio , Pericardial Effusion , Pericardiocentesis , Stroke , DabigatranABSTRACT
OBJECTIVE: To prepare porous starch foam to improve the solubility and dissolution rate of dabigatran etexilate. METHODS: Porous starch foam (PSF) was synthesized as a carrier by solvent exchange method. Dabigatran etexilate (DE) was loaded onto the nanopores of PSF by solvent evaporation method. Scanning electron microscopy was used for investigating the morphology and structure of PSF. The dispersal state of DE in drug-loaded sample (PSF-DE) was determined by differential scanning calorimetry, powder X-ray diffraction and fourier transform infrared spectroscopy. The dissolution rate was measured by in-vitro dissolution experiment. RESULTS: Porous starch foam was prepared successfully and the spatial restriction of nanopores effectively suppressed crystal-linity of dabigatran etexilate as shown by structure characterization. The in-vitro dissolution experiment showed that the dissolution rate; of dabigatran etexilate was improved significantly. CONCLUSION: Porous starch foam can improve the hydrophilicity of the poorly water-soluble drug dabigatran etexilate.
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Thrombo-embolic disease is a major challenging clinical problem associated with significant mortality and morbidity. Anticoagulation with the existing heparin products and vitamin K antagonist (VKA) anticoagulants are still the mainstay of management. However, due to the risk of bleeding and well-documented drawbacks, the quest for a novel oral anticoagulant has led to the clinical development of dabigatran etexilate. Dabigatran etexilate is a direct thrombin (IIa) inhibitor which has recently been approved in India for prevention of venous thromboembolic events (VTE) in patients who have undergone major orthopaedic (total knee or hip replacement) surgery and for prevention of stroke, systemic embolism and reduction of vascular mortality in adult patients with atrial fibrillation. Thus dabigatran etexilate is a promising alternative to the current heparin products and VKAs in patients who require long-term oral anticoagulation.