DRUG METABOLISM AND DISPOSITION
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2019
·Vol. 47
·期 12
·1425-1432
·
IF 3.354
Hongqiu Zhou,Li Yang,Changsuo Wang,Zhiqiang Li,Zhen Ouyang,Mangting Shan,Jun Gu,Yuan Wei
Rat CYP2D1 has been considered as an ortholog of human CYP2D6. To assess the role of CYP2D1 in physiologic processes and drug metabolism, a CYP2D1-null rat model was generated with a CRISPR/Cas9 method. Seven base pairs were deleted from exon 4 of CYP2D1 of Sprague-Dawley wild-type (WT) rats. The CYP2D1-null rats were viable and showed no abnormalities in general appearance and behavior. The metabolism of venlafaxine (VLF) was further studied in CYP2D1-null rats. The Vmax and intrinsic clearance of the liver microsomes in vitro from CYP2D1-null rats were decreased (by ∼46% and ∼57% in males and ∼47% and ∼58% in females, respectively), while the Michaelis constant was increased (by ∼24% in males and ∼25% in females) compared with WT rats. In the pharmacokinetic studies, compared with WT rats, VLF in CYP2D1-null rats had significantly lower apparent total clearance and apparent volume of distribution (decreased by ∼36% and ∼48% in males and ∼23% and ∼25% in females, respectively), significantly increased area under the curve (AUC) from the time of administration to the last time point, AUC from the start of administration to the theoretical extrapolation, and Cmax (increased by ∼64%, ∼59%, and ∼26% in males and ∼43%, ∼35%, and ∼15% in females, respectively). In addition, O-desmethyl venlafaxine formation was reduced as well in CYP2D1-null rats compared with that in WT rats. Rat depression models were developed with CYP2D1-null and WT rats by feeding them separately and exposing them to chronic mild stimulation. VLF showed better efficacy in the WT depression rats compared with that in the CYP2D1-null rats. In conclusion, a CYP2D1-null rat model was successfully generated, and CYP2D1 was found to play a certain role in the metabolism and efficacy of venlafaxine.
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PubMed
高影响因子
Analytical Methods
·
2019
·Vol. 12
·期 2
·141-148
·
IF 2.378
Xue Ren,Man He,Beibei Chen,Bin Hu
Herein, magnetic porous organic polymers (MOPs) prepared via an azo coupling reaction in water under mild conditions are evaluated for the extraction of seven cardiovascular drugs, including xylocaine, metoprolol, mexiletine, labetalol, propranolol, carvedilol and propafenone, from human urine samples for the first time. The extraction mechanisms are assumed to be electrostatic interaction and π–π stacking. The MOPs exhibited fast adsorption/desorption time (13 min) and high enrichment factors (315–365-fold) for target analytes. Based on this, a method coupling magnetic solid phase extraction with HPLC-UV detection was developed for the analysis of cardiovascular drugs. Under the optimized conditions, the LODs (S/N = 3) were in the range of 0.06–0.57 μg L−1 with an RSD (n = 5) of 4.3–8.6%, and the linear range was 0.2–200 μg L−1 for propranolol, 2–200 μg L−1 for metoprolol, and 0.5–200 μg L−1 for the other five analytes. The developed method was applied for the analysis of cardiovascular drugs in urine samples with recoveries of 89.0–112%. In order to further evaluate the application potential of this method, real-time monitoring of metoprolol in urine samples collected from volunteers treated with metoprolol tablets was performed. The proposed method is simple, fast, and sensitive and has good potential in the monitoring of cardiovascular drugs in competitive sports and clinical analysis.
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高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2016
·
IF 3.926
Wenying Fan,Man He,Linna You,Xuewei Zhu,Beibei Chen,Bin Hu
Due to the high selectivity and stability, molecularly imprinted polymers (MIPs) have been successfully applied in stir bar sorptive extraction (SBSE) as a special coating to improve the selective extraction capability for target analytes. However, traditional MIPs usually suffer from incompatibility in aqueous media and low adsorption capacity, which limit the application of MIP coated stir bar in aqueous samples. To solve these problems, a water-compatible graphene oxides (GO)/MIP composite coated stir bar was prepared in this work by in situ polymerization. The prepared water-compatible GO/MIP coated stir bar presented good mechanical strength and chemical stability, and its recognition ability in aqueous samples was improved due to the polymerization of MIP in water environment, the adsorption capacity for target analytes was also increased by the addition of GO in MIP pre-polymer solution. Based on it, a method of water-compatible GO/MIP coated stir bar sorptive extraction combined with high performance liquid chromatography-ultraviolet detector (HPLV-UV) was proposed for the analysis of propranolol (PRO) in aqueous solution. The influencing factors of SBSE, such as sample pH, salt effect, stirring rate, extraction time, desorption solvent and desorption time, were optimized, and the analytical performance of the developed SBSE-HPLC-UV method was evaluated under the optimized conditions. The limit of detection (LOD) of the proposed method for PRO was about 0.37 μg L −1 , and the enrichment factor (EF) was 59.7-fold (theoretical EF was 100-fold). The reproducibility was also investigated at concentrations of 5 μg L −1 and the relative standard deviation (RSD) was found to be 7.3% (n = 7). The proposed method of GO/MIP coating-SBSE-HPLC-UV was successfully applied for the assay of the interested PRO drug in urine samples, and further extended to the investigation of the excretion of the drugs by monitoring the variation of the concentration of PRO in urine within 10 h after drug-taking.
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PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Xiaofeng Wu,Wenqi Liu,Shuyi He,Linyu Long,Hongxu Peng,Li Yang,Yunbing Wang
Myocardial infarction (MI) is the leading cause of death worldwide. Studies have shown that ischemia, oxidative stress, and prolonged inflammation are the main reasons that hinder cardiac tissue repair. In such situation, the present study introduced a methacrylate gelatin (GelMA) / thiolated hyaluronic acid (HASH) hydrogel loaded with deferoxamine (DFO) and carvedilol (GelMA/HASH@DPDCNs) for MI treatment. The prepared hydrogel had good injectable properties, and could continuously release DFO and carvedilol. The results of in vitro cell experiments showed that hydrogel could effectively reduce reactive oxygen species (ROS) levels, and apoptosis in cardiomyocytes. And in the LPS-induced macrophage polarization model, the hydrogel could also effectively reduce the expression of pro-inflammatory factors TNF-α and IL-6, and increase the expression level of IL-10, thereby inhibiting the inflammatory response. In addition, the hydrogel could promote endothelial cell proliferation, migration, and tube formation, with the potential to promote angiogenesis. In the rat model of acute MI, the prepared hydrogel could accelerate the repair of damaged myocardium by anti-apoptosis, inhibiting inflammation, and promoting angiogenesis. We expect that the results of this study will provide a novel, and effective strategy for the clinical treatment of MI.
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高影响因子
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