JOURNAL OF MOLECULAR STRUCTURE
·
2016
·
IF 1.78
Yanlei Kang,Jianming Gu,Xiurong Hu
Febuxostat was investigated due to its significant effect in the treatment of gout. However, its poor water solubility hinder its potential applications. In recent years, cocrystals have increasingly being applied to enhance the drug solubility . To improve the solubility, two cocrystals of Febuxostat were synthesized through the method of cooling crystallization. The prepared cocrystals febuxostat-isonicotinamide(FEB-INA) and febuxostat-arginine(FEB-Arg) were studied by microscopical observation, Powder X-Ray Diffraction(PXRD), Single Crystal X-ray Diffraction, Differential Scanning Calorimetry(DSC), and infrared spectrometry . At the same time, the cocrystals' solubility and dissolution rate were explored. Both the cocrystals showed higher solubility compared to the pure drug. The FEB-Arg cocrystal enhanced about 900 times of solubility compared to the pure drug. The current study proved that cocrystallization can be a better way to enhance the solubility of the poorly water-soluble drug.
研究领域:
药物化学
·
材料科学
·
药剂学
✓ 已验证
产品关联
DOI
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2019
·Vol. 33
·期 9
·e4568
·
IF 1.748
Liping Zhou,Hexiang Liu,Zhongyong Xu,Su Guan,Lei Zhang
Febuxostat is a novel nonpurine type of highly selective xanthine oxidoreductase inhibitor. A rapid and sensitive ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry method for simultaneous separation and determination of febuxostat and its metabolites in rat serum and urine was developed at various time points after oral administration to the rats. The febuxostat metabolites were predicted by biotransformation software and transformed to a personal compound database to quickly determine the possible metabolites from the MS1 data. The possibility of the MS/MS fragmentation was calculated by the Molecular Structure Correlator software. As a result, five phase I and two phase II metabolites in rat serum, and seven phase I and three phase II metabolites in rat urine were identified, of which four metabolites (M2, M5, M6, M7) have not been reported before. The metabolite toxicities are predicted, and the results are helpful for the design of new xanthine oxidoreductase inhibitors.
研究领域:
药理学
·
分析化学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS
·
2022
·
IF 1.449
Xin-Yan Lu,Yan-Yue Lou,Kai-Li Zhou,Shao-Liang Jiang,Jie-Hua Shi
In this paper, the interacting characteristics of febuxostat (FBST), an inhibitor of xanthine oxidase for treating gout patients with hyperuricemia with calf thymus DNA (ctDNA) was investigated through multi-spectroscopic methodologies combined with theoretical calculation for understanding the interacting mode on ctDNA, affinity with ctDNA, interacting forces, as well as the alteration in the conformation of ctDNA after interacting FBST The experimental results demonstrated that interacting FBST with ctDNA formed 1:1 complex, the association constant was 913 M−1 at 298 K, suggesting the affinity of FBST on ctDNA was very weak, the interacting mode of FBST on ctDNA was groove binding, and it inserted into the minor groove with rich A-T region of ctDNA. Based on the results of the thermodynamic analysis and theoretical calculation, it can be inferred that the dominated interacting forces between FBST and ctDNA were van der Waals forces and hydrogen bond. And, interacting FBST with ctDNA was a spontaneous, enthalpy-driven, and exothermic process because of ΔG0 < 0, ΔH0 < 0, and |ΔH0| > T|ΔS0|. The results of the circular dichroism (CD) measurements indicated the conformation of ctDNA was weakly disturbed after interacting with FBST but still maintained B-conform. The studied results offer significant insight into further clarifying whether it has genotoxicity.
研究领域:
生物化学
·
药物化学
·
分子生物学
✓ 已验证
DOI
高影响因子
ARCHIV DER PHARMAZIE
·
2026
·Vol. 359
·期 6
·e70263
·
IF 3.5
Yao Lu,Han Wang,Dong Yan,Baoyu He,Jingjing Guo,Xixi Hou,Ling Liu
Febuxostat, a selective xanthine oxidase inhibitor, was modified via 1,2,3-triazole-based molecular hybridization to generate a series of derivatives with potential anticancer activity. Among them, compounds 8c and 8e exhibited significant antitumor effects across multiple cancer cell lines, particularly in HepG2 cells, with IC 50 values of 6.96 ± 1.76 and 8.56 ± 1.93 μM, respectively. Colony formation assays confirmed that both compounds markedly inhibited tumor cell proliferation. Annexin V-FITC/PI and TUNEL assays further demonstrated that 8c and 8e induced DNA damage and apoptosis in HepG2 cells, as shown by increased γ-H2AX expression and enhanced DNA strand breaks. They also activated intrinsic apoptotic pathways, including the cleavage and activation of caspase-9, caspase-3, and PARP. In vivo, nude mouse xenograft experiments validated their antitumor efficacy, with elevated cleaved caspase-3 levels in tumor tissues. Collectively, these findings indicate that 8c and 8e possess strong therapeutic potential against liver cancer and exhibit promising efficacy and safety profiles.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MICROENCAPSULATION
·
2018
·
IF 1.793
Jingjing Tang,Jiayin Bao,Xiangjun Shi,Xiaoxia Sheng,Weike Su
The research aimed to prepare febuxostat (FEB) solid dispersion through solvent evaporation. Optimised solid dispersion composed of FEB, polyvinylpyrrolidone (PVP K30) and poloxamer at a ratio of 1:3:3 was characterised. Powder X-ray diffraction (XRD) and differential scanning calorimetry (DSC) indicated FEB was transformed from crystalline into the amorphous state in solid dispersion and scanning electron microscopy (SEM) revealed the morphology. Fourier transform infrared spectroscopy (FT-IR) suggested the interactions formed between FEB and polymers. A remarkable increase was observed of the optimised formulation in saturation solubility, dissolution studies (96.17 ± 0.79% in pH 6.0), and bioavailability (Cmax 18.25 ± 2.44 vs. 7.72 ± 0.48 μg/mL and AUC0–∞ 53.62 ± 7.63 vs. 34.76 ± 2.45 μg·h/mL). Besides, the FEB solid dispersion showed great stability after 90 days storage. Thus, the present study supports the rationality of PVP K30 and poloxamer188 as co-carriers for the preparation of FEB solid dispersion.
研究领域:
药学
·
药物递送系统
·
药剂学
✓ 已验证
DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Jiaqi Wen,Shuling Chen,Le Deng,Xinru Chen,Xiaoyu Jiang,Xing Hu,Deming Gong,Guowen Zhang
The development of natural xanthine oxidase (XO) inhibitors is an effective strategy for the treatment of hyperuricemia. In this study, the inhibition mechanism of phloretin on XO and its joint inhibition with clinical drugs (allopurinol and febuxostat) were investigated, using multispectroscopic and molecular simulation techniques. The results showed that phloretin reversibly inhibited XO in a mixed type with an IC 50 value of 31.83 ± 0.32 μM. Phloretin quenched the fluorescence of XO with a static mechanism and hydrophobic interactions were the key binding force of phloretin binding to XO. Furthermore, the interaction between phloretin and XO resulted in a more relaxed structure and less stable of the enzyme with a reduction in the α-helix content from 21.5% to 11.3%. The heatmap analysis showed that a combination of phloretin (15 μM) and allopurinol (10 μM) or phloretin (30 μM) and febuxostat (0.01 μM) exhibited the strongest synergistic effect on XO inhibition in a mixed manner. The combination of phloretin and allopurinol/febuxostat enhanced the binding affinity with XO compared to the inhibitors individually. Molecular docking indicated that phloretin, allopurinol and febuxostat bound to different sites of XO to produce a synergistic inhibition by preventing substrate access to the Mo activity center and affecting electron transfer. This study may provide theoretical references for the development of phloretin and its formulation with clinical drugs as uric acid-lowering food functional factor or drug.
研究领域:
药理学
·
生物化学
·
分子生物学
·
药物开发
✓ 已验证
产品关联
DOI
高影响因子
ELECTROANALYSIS
·
2022
·Vol. 35
·期 4
·e202200403
·
IF 3.077
Fuxin Liu,Tianyi Shang,Lingling Han,Nan He,Xiuhui Liu
Xanthine is a significant biomolecule and its concentration level in urine and blood plasma is an indicator of specified pathological states. Here, a new sensing platform was designed, which showed excellent analytical performance for xanthine. Importantly, it is the first time to investigate the kinetics of xanthine metabolic reaction by electrochemical method. The results demonstrated that the conversion of xanthine to uric acid completely conformed to the Michaelis-Menten kinetics. Furthermore, we also studied the inhibitory effect of febuxostat on xanthine oxidase activity detailed. As expected, the work may offer potential value for researchers in the treatment of hyperuricemia and gout.
研究领域:
生物化学
·
医学
·
药物研究
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2025
·
IF 4.7
Ningzi Guo,Zhenhua Liu,Yanling Wu,Song Yuan,Ningyi Wei,Yang Liu,Hui Xu,Hua Chen
Febuxostat (FEB), a primary long-term therapy for managing gout and chronic hyperuricaemia, has limited clinical application primarily due to its low aqueous solubility. This limitation necessitates high-dose administration, thereby increasing the risk of cardiovascular mortality. To address the solubility challenge, a natural bioactive alkaloid aloperine (ALO) was used as a co-former to form FEB-ALO, a co-amorphous system of FEB and ALO at a 1:1 molar ratio using both solvent evaporation and the liquid-assisted grinding method. Structural characterisation was performed using powder X-ray diffraction, Fourier transform infrared spectroscopy (IR), differential scanning calorimetry, and nuclear magnetic resonance spectroscopy (NMR). Dissolution behaviours, such as equilibrium solubility and the intrinsic dissolution rate, were also investigated. FEB-ALO showed a greatly enhanced intrinsic dissolution rate (145-fold) and water solubility (>10,000-fold) compared to those with the crystalline form A of FEB. Integrating IR, NMR and molecular electrostatic potential surface analysis revealed that robust ionic and hydrogen-bonding interactions within the FEB-ALO co-amorphous system explained the enhanced dissolution performance.Molecular docking and dynamic simulations further demonstrated the strong affinity and binding stability of FEB-ALO to xanthine oxidase, suggesting its promising efficacy in the treatment of hyperuricaemia and gout. The findings presented herein indicate that the drug-drug co-amorphous system holds promise for optimising the FEB dosage and proposing a synergistic drug combination approach.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Pharmaceutics-X
·
2023
·
IF 4.7
Junpeng Sun,Jiaqun Du,Xiaobang Liu,Jinyu An,Yingqiao Li,Yanan Yu,Minghui Li,Li Zheng,Chao Wu,Lili Hu
The aim of this study was to design a chitosan-coated hollow tin dioxide nanosphere (CS-HSn) for loading febuxostat (FEB) using an adsorption method to obtain a sustained-release system (CS-HSn-FEB) to improve the oral bioavailability of FEB. The morphological characteristics of hollow tin dioxide nanospheres (HSn) and CS-HSn were analyzed by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The hemolysis test and CCK-8 test were used to assess the biosafety of HSn and CS-HSn. Powder X-ray diffraction (PXRD) and differential scanning thermal analysis (DSC) were performed on CS-HSn-FEB to analyze the drug presence status. The dissolution behavior and changes in plasma drug concentration of CS-HSn-FEB were evaluated in vitro and in vivo. Sections of intestinal tissues from SD rats were obtained to observe whether chitosan could increase the distribution of nanoparticles in the intestinal tissues. The results showed that FEB was present in CS-HSn in an amorphous state. Moreover, CS-HSn, with good biosafety, significantly improved the water solubility and oral absorption of FEB, indicating that CS-HSn has great potential to improve the intestinal absorption and oral bioavailability of insoluble drugs.
研究领域:
药剂学
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL BIOLOGY AND MEDICINE
·
2023
·
IF 3.2
Jinhong Tian,Shuaishuai Zhang,Lu Li,Xueman Lin,Yongmei Li,Kunlu Zhao,Fengxin Zheng,Yongjun Chen,Yang Yang,Ting Wu,Jianxin Pang
Excessive acetaminophen (APAP) application is a major cause of drug-induced liver injury (DILI). Febuxostat (Feb), a drug for reducing uric acid (UA) levels, was demonstrated to relieve hepatic inflammation and reverse organ functions. However, the effect of Feb on APAP-induced DILI and its mechanisms have not been fully explored. In this study, Feb (10 mg/kg) was given to mice by gavage 1 h after APAP (300 mg/kg, i.g.) induction. Serum and liver samples were collected 12 or 3 h after APAP challenge. Feb treatment was found to remarkably improve APAP-induced DILI, as evidenced by reduced serum ALT, AST and UA levels, pathomorphology, inflammatory, and oxidative responses. Consistently, treatment with Feb also reduced the cell injury induced by APAP in LO2 cells. Mechanistically, Feb induced GPX4 expression, activated the Keap1/Nrf2 pathway, and inhibited the TLR4/NF-κB p65 pathway. Feb also inhibited glutathione (GSH) depletion and Jun N-terminal kinase (JNK) activation in the early injury phase. Notably, pretreatment with Feb for 3 days also revealed preventive effects against APAP-induced DILI in mice. Overall, our data revealed a potential health impact of Feb on APAP-mediated DILI in vivo and in vitro, suggesting that Feb might be a potential candidate for treating DILI.
✓ 已验证
DOI
PubMed
高影响因子
PHARMAZIE
·
2013
·Vol. 68
·期 6
·396-400
·
IF 0.962
Shi Zheng,Liu Jian,Hu Xing-Jiang,ShenTu Jian-Zhong
The purpose of this study was to design a simple, sensitive and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for a febuxostat bioequivalence study in healthy Chinese male volunteers. In this method, febuxostat and etodolac (internal standard) were isolated
from plasma samples by protein precipitation with acetonitrile. The supernatant was chromatographed on a Zorbax SB-C18 (150 × 3.0 mm, 3.5-μm particle size, Agilent) column with a SecurityGuard Inertsil Symmetry C18 column (12.5 × 4.6 mm, 5-μm particle size, Waters). The lower
limit of quantification for febuxostat in 0.2 mL of human plasma was 13.40 ng•mL–1, and the linearity was achieved over a concentration range from 13.40 to 21440 ng•mL–1. Febuxostat tablets from Hengrui Medicine Co., Ltd (test, Jiangsu, China) and
from Takeda pharmaceuticals america, Inc. (reference, Deerfield, IL) were evaluated following a single 80 mg oral dose to 18 healthy volunteers. Bioequivalence was determined by calculating 90% confidence intervals (90% CI) for the ratio of C
max, AUC
0-t,
and AUC
0-∞ values for the test and reference products, using logarithmic transformed data. The calculated 90% CIs for the ratio of C
max (88.7∼131.2%), AUC
0-t (99.2∼ 122.7%) and AUC
0-∞ (99.5∼123.1%)
values for the test and reference products were all located within the bioequivalence criteria range (80∼125% for AUC, and 70∼143% for C
max), proposed by State of Food and Drug Administration [SFDA, 2005. China]. It was concluded that the two febuxostat formulations
(test and reference) analyzed were bioequivalent in terms of rate and extent of absorption and the method met the principle of quick and easy clinical analysis.
研究领域:
药理学
·
分析化学
·
临床药学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）