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Table of Content

    Volume 28 Issue 10
    26 October 2023
    Effects and mechanism of Ginseng Yixin granules (QSYXG) for heart failure with preserved ejection fraction based on the network pharmacology and molecular docking strategy
    CHEN Yulin, JIANG Hugang, WANG Xinqiang, LIU Kai, LI Yingdong, AN Tao, ZHAO Xinke
    2023, 28(10):  1081-1092.  doi:10.12092/j.issn.1009-2501.2023.10.001
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    AIM: To study the mechanism of Ginseng Yixin granules (QSYXG) in treating ejection fraction preserved heart failure (HFpEF) based on network pharmacology. METHODS: Effective chemical composition information of QSYXG particles was collected through TCMSP database; DisGeNET, GeneCards, OMIM database for obtaining HFpEF related targets; Metascape GO and KEGG enrichment analysis of the intersection targets of HFpEF; STRING Construction and analysis of the database PPI network; Cytoscape3.7.2 Software construction network diagram; Docking of the major active components to the core target with the AutoDock Vina software molecules, the results were visualized and analyzed with pymol. RESULTS: A total of 66 components and corresponding targets were obtained, HFpEF corresponds to 1 931 targets, The intersection of 127 targets, the main active ingredients are quercetin, kaempferol, β-sitosterol, etc.; TNF, AKT1, IL-6, P53 and JUN as the core targets, Good docking of the key components with the core targets; Mainly involving the positive regulation of gene expression, signal transduction, negative regulation of apoptotic process, positive regulation of cell proliferation and senescence, hypoxia response, negative regulation of gene expression, inflammatory response and so on, PI3K-Akt, AGE-RAG, MAPK, TNF, IL-17, and HIF-1 are the main associated signaling pathways. CONCLUSION: QSYXG may treat HFpEF by activating targets of TNF, AKT1, IL-6, P53, JUN, and regulating apoptotic process, cell proliferation, hypoxia response, and inflammatory response.
    3-bromopyruvate cholesterol ester enhances the sensitivity of breast cancer cells to tamoxifen 
    WANG Xiu, JI Qilin, PEI Wenjun, ZENG Ying
    2023, 28(10):  1093-1100.  doi:10.12092/j.issn.1009-2501.2023.10.002
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    AIM: To investigate the effect of 3-bromopyruvate cholesterol ester (3-BP-Cl) on the sensitivity of breast cancer to tamoxifen (TAM). METHODS: MTT assay and Calcein AM/PI staining were used to detect the effect of drugs on the viability of breast cancer cells. Kim's formula was used to detect synergistic anti-breast cancer effect of cholesterol 3-bromopyruvate and tamoxifen. The inhibitory effect of drugs on proliferation of breast cancer cells was detected by colony-forming assay. Flow cytometry was used to detect the apoptosis of breast cancer cells. Western blot assay was used to detect the expression of hexokinase 2, Bcl-2 and Bax proteins. RESULTS: MTT results showed that combination 3-BP-Cl and TAM could significantly inhibit the activity of MCF-7 cells (P<0.05). The results of King's formula showed that 3-BP-Cl and TAM had synergistic inhibitory effect on the proliferation of MCF-7 cells (q>1.15). Calcein AM/PI staining showed that the number of dead cells was the highest in the combination group. Colony-forming assay showed that the combination group had stronger inhibitory effect on the proliferation of MCF-7 cells than that of single drug groups. AnnexinV flow cytometry results showed that, the cell apoptosis in the combination group was significantly increased (P<0.01). Western blot results showed that 3-BP-Cl inhibited the expressions of hexoktokinase 2 and Bcl-2, and enhanced the expression of Bax in MCF-7 cells. CONCLUSION: 3-BP-Cl could increase the sensitivity of breast cancer cells to tamoxifen, and synergically inhibit the proliferation of breast cancer cells. The mechanism is possibly related to its effects of inhibiting the expression of HK2/Bcl-2, and enhancing the expression of Bax. 
    Propofol relieves the subcutaneous chloroquine-induced pruritus in rats via TRPV1 and CB1 receptors of spinal cord
    HENG Bingbing, YANG Danfeng, DAI Shuyang, SHANGGUAN Wangning
    2023, 28(10):  1101-1108.  doi:10.12092/j.issn.1009-2501.2023.10.003
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    AIM: To explore the possible mechanism of propofol in alleviating pruritus induced by subcutaneous injection of chloroquine in rats. METHODS: The pruritus model of chloroquine in SD rats was established and the administration time was determined. 18 rats with successful pruritus model induced by subcutaneous injection of chloroquine were randomly divided into NS group, I group and P group. Normal saline 80 μL/kg, fat emulsion 80 μL/kg and propofol 0.8 mg/kg were injected through internal jugular vein catheter 5 minutes after subcutaneous injection of chloroquine. Another 6 rats were randomly selected as group C, and the same volume of normal saline as the other 3 groups was injected subcutaneously in the back of the neck and through the internal jugular vein catheter. The rats were killed 16 minutes after the corresponding drugs were injected into the internal jugular vein. The expressions of TRPV1 and CB1 receptors in the spinal cord were detected by Western blot. RESULTS: Compared with NS group and I group, the expression level of TRPV1 receptor in the spinal cord of P group rats was significantly increased (P<0.01), while there was no statistically significant difference between C group, NS group, and I group; The expression level of CB1 receptor was significantly higher than that of group C, NS, and I (P<0.05), while there was no statistically significant difference between group C, NS, and I. CONCLUSION: Propofol can significantly alleviate pruritus caused by subcutaneous injection of chloroquine in rats, which may exert an antipruritic effect by increasing the expression of TRPV1 and CB1 receptors in the spinal cord of rats.
    Drug-induced dysphagia risk in elder people——A pharmacovigilance study of FDA Adverse Event Reporting System (FAERS) database
    JIA Boying, ZHOU Shuang, WAN Liyan, ZHOU Ying, CUI Yimin
    2023, 28(10):  1109-1120.  doi:10.12092/j.issn.1009-2501.2023.10.004
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    AIM: To evaluate the risk of drug-related dysphagia in elder people based on the FDA Adverse Event Reporting System (FAERS). METHODS: We collected the reports of dysphagia in elder people (Age≥65) from 2004 quarter 1 through 2022 quarter 2 of FAERS by Open Vigil 2.1 database. The reported odds ratio (ROR) and the proportional reported ratio (PRR) were calculated to detect the adverse reaction signal of drug-induced dysphagia in elder people. Signal generation standard of ROR: number of reports≥3 with the lower limit of 95% confidence interval (CI) of the ROR value>1, PRR≥2 and c2≥4, which indicates positive signal. RESULTS: A total of 51, 590 reports (including 13,197 dysphagia events and 1,395 drug) were considered, and 350 positive signal drugs were detected. The Median age of the included patients was 75 years,and there were more females than males. Positive signal drugs are mainly concentrated on nervous system [n=99, ROR 2.17(1.97-2.39)] , alimentary tract and metabolism [n=47, ROR 1.44(1.25-1.66)], cardiovascular system [n=42, ROR 1.30(1.22-1.39)], anti-infectives for systemic use [n=27, ROR 1.44(1.29-1.61)]. CONCLUSION: Drug-induced dysphagia risk are widespread according to the FAERS. It is recommended that multidisciplinary teams should assess the swallowing status of potients when selecting drugs. For elderly patients with high risk of swallowing, priority should be given to drugs with negative signals of dysphgia. When the preferred  drugs fail to meet the clinical need, it is recommended to select drug with lowe risk.Simultaneous clinical need to supervise the application of drugs in the process to prevent the occurrence of dysphagia events.
    A bioequivalence study of generic and brand clozapine in schizophrenic patients
    LI Xuejing, JIANG Jinping, LI Sining, WAN Linfei, ZHOU Xiangxiang, YANG Lian, LAN Ke
    2023, 28(10):  1121-1130.  doi:10.12092/j.issn.1009-2501.2023.10.005
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    AIM: To establish a ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to determination the plasma concentration of clozapine and compare the bioequivalence of a generic clozapine tablet with Clozaril?. METHODS: A randomized, open-label, multiple-dose, steady-state, two-treatment, two-period, crossover study was conducted on Schizophrenia patients who had been receiving a stable dose of clozapine for at least three months under fasting condition. Twenty-four schizophrenia patients were orally administrated with Clozaril tablets or the generic clozapine tablet 100 mg every 12 h for 10 days, then switched to the other formulation for the next 10 d. The concentrations of clozapine in plasma were determined by an estabilished UPLC-MS/MS method. RESULTS: The method was validated by investigating the accuracy and precision for intra and inter-day runs in a linear concentration from 5-2 000 ng/mL. The main pharmacokinetic parameters of test and reference formulation in plasma were shown as follows: Tmax,ss were (1.01-5.02) and (1.00-5.00) h;Cmax,ss were (665.0 ± 279.3) and (679.5 ± 240.3) ng/mL; AUC0-τ were 
    (5 408.1 ± 2 918.2) and (5 389.5 ± 2 223.6) ng?h?mL-1, respectively. The 90% confidence intervals (CIs) for the natural logarithmically transformed Cmax,ss and AUC0-τ ratios were 86.15%-106.25% and 87.69%-104.51% under fasting condition. Safety/tolerability profiles were similar between formulations. CONCLUSION: The two tablet formulations are bioequivalent in Chinese subjects.
    Safety analysis on bioequivalence studies of orally inhaled drug products in healthy Chinese subjects#br#
    LIU Min, KONG Xiang, ZHANG Ye, GU Yifei, XIANG Xuemei, HUANG Kai
    2023, 28(10):  1131-1138.  doi:10.12092/j.issn.1009-2501.2023.10.006
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    AIM: To investigate the safety of bioequivalence (BE) studies of orally inhaled drug products (OIDPs) conducted by Phase I clinical Research Center of our hospital. METHODS: The safety data were collected from 482 healthy subjects enrolled in 20 OIDPs BE studies in Wuxi People's hospital from 2017 to 2022. The difference of adverse events (AEs) between test preparation and reference preparation were compared, as well as the influence of gender, age, mechanism of drug action and device type on AE were analyzed. RESULTS: A total of 102 cases of AEs were occurred in 77 subjects (16.0%, 77/482), 87 cases of AEs were related to experimental drugs, all AEs were mild or moderate, and no serious adverse events occurred. There was no difference in the incidence of AE between test preparation and reference preparation. In addition, gender, age, mechanism of drug action and device type had no significant effects on AEs. CONCLUSION: In 20 bioequivalence studies of OIDPs, OIDPs were safe and well tolerated in healthy subjects after dosing, and safety features of generic OIDPs and original drug were basically similar.
    Effect of augmented renal clearance (ARC) on the pharmacokinetics, efficacy, and safety of vancomycin in patients with infective endocarditis
    WU Lili, LIANG Zhi, HUANG Siyong, WANG Yan
    2023, 28(10):  1139-1145.  doi:10.12092/j.issn.1009-2501.2023.10.007
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    AIM: To study the effects of augmented renal clearance (ARC) on vancomycin pharmacokinetics, efficacy, and safety in patients with infective endocarditis, so as to provide better guidance for vancomycin medication. METHODS: The retrospective analysis was conducted. Patients data from the hospital medical record system from April 2020 to April 2023 during the cardiovascular surgery with use of vancomycin were collected. The subjects were divided into normal group and ARC group according to glomerular filtration rate (eGFR). According to the population pharmacokinetic model, the measured trough concentration was used for a Bayesian approach to estimate individual pharmacokinetic parameters and analyze influence of ARC on vancomycin pharmacokinetics. RESULTS: A total of 163 patients were included in this study. The incidence of ARC was 23.31%. The age of patients in ARC group was significantly lower than that in normal group  (P<0.05).  Moreover, the steady-state trough concentration (Cmin), trough concentration compliance rate, area under the curve (AUC), and elimination half life (t1/2) were significantly lower in ARC group than that in normal group (P<0.05). In addition, ARC group had significantly higher clearance (CL) and elimination rate than normal group (P<0.05). Correlation analysis showed that Cmin was positively correlated with AUC (r2=0.943, P<0.01 in normal group; r2 = 0.918, P<0.01 in ARC group). The trough concentration threshold corresponding to AUC> 400 mg·h·L-1 in normal group and ARC group were 12.78 mg/L and 13.32 mg/L, respectively. There was no significant difference in terms of clinical effectiveness between the two groups. Adverse reactions occurred in 15 patients in the normal group and 8 patients in the ARC group. CONCLUSION: ARC significantly affects the trough concentration, trough concentration compliance rate, and pharmacokinetic process of vancomycin  in patients with infective endocarditis. It is recommended to monitor and optimize vancomycin dosage regimen in patients with  infective endocarditis according to different renal function status and therapeutic drug monitoring for the purpose to facilitate individualized treatment.
    BCG + piroxicam versus BCG + gemcitabine for prevention of postoperative recurrence in intermediate- and high-risk bladder cancer and effects on serum AGR and PON1
    ZHANG Wei, WANG Hongyuan, LEI Xiaohang, ZHAO Yingshuai, LV Weichao, ZHANG Jianguo
    2023, 28(10):  1146-1153.  doi:10.12092/j.issn.1009-2501.2023.10.008
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    AIM: To investigate the effect of BCG + piroxicam versus BCG + gemcitabine in the prevention of postoperative recurrence in intermediate- to high-risk bladder cancer and the effect on serum albumin/globulin ratio (AGR) and paraoxonase 1 (PON1). METHODS: Eighty patients with medium-high risk bladder cancer in our hospital from October 2021 to April 2022 were randomly divided into two groups with 40 cases each. Both groups received transurethral resection of bladder tumor. The control group received postoperative bladder perfusion of pirubicin combined with BCG vaccine, and the study group received postoperative bladder perfusion of gemcitabine combined with BCG vaccine. The therapeutic effect, serum tumor markers [secretory protein Dickkopf (DKK), bladder cancer specific nuclear matrix protein-1 (BLCA-1), β2-microglobulin (β2-MG)], new angiogenesis factors [vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)], AGR and PON were compared between the two groups 1. Level, quality of life [Core Quality of Life Questionnaire Scale (EORTC QLQ-C30)], functional status [Functional status Scoring Scale (KPS)], adverse reactions, The recurrence rates at 1 year after surgery were compared between the two groups. RESULTS: The total effective rate of the study group was 92.50%(37/40) higher than that of the control group 75.00%(30/40) (P<0.05). The serum levels of DKK, BLCA-1, β2-MG, VEGF, FGF and AGR in the study group were lower than those in the control group at 1 month, 3 months and 6 months after surgery, while the level of PON1 was higher than that in the control group (P<0.05). The EORTC QLQ-C30 and KPS scores of the study group were higher than those of the control group at 1, 3 and 6 months after surgery (P<0.05). The incidence of nausea/vomiting, diarrhea, leukopenia and cystitis in the study group was lower than that in the control group (P<0.05). The recurrence rate of the study group 1 year and 2 years after surgery was lower than that of the control group (P<0.05). CONSLUSION: Compared with pirubicin combined with BCG vaccine, gemcitabine combined with BCG vaccine is more effective in the treatment of middle and high-risk bladder cancer, which can inhibit tumor angiogenesis, regulate AGR and PON1 levels, prevent postoperative recurrence, improve quality of life, improve functional status, and have higher safety.
    Application of remimazolam combined with propofol in painless endoscopic retrograde cholangiopancreatography
    ZHENG Hongbo , YAO Wenlong , LUO Ailin, ZHOU Biyun
    2023, 28(10):  1154-1160.  doi:10.12092/j.issn.1009-2501.2023.10.009
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    AIM: To observe and compare the clinical efficacy and safety of remimazolam and propofol alone and in combination in endoscopic retrograde cholangiopancreatography (ERCP) anesthesia. METHODS: A total of 120 patients undergoing elective ERCP were divided into the propofol group (P group), the remimazolam group (R group), and the remimazolam combined with propofol group (RP group) according to a random number table, with 40 patients in each group, and the three groups completed anesthesia according to the designated drug regimen (propofol in group P; remimazolam in group R; and remimazolam combined with propofol in group RP). General information, operation time and awakening time of the patients in the three groups were compared, as well as oxygen saturation (SpO2), heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), electroencephalography bifrequency index (BIS), and Ramsay's sedation score before anesthesia (T0), after anesthesia (T1), at the time of placement of the scope (T2), duodenal papillotomy (T3), and stenting or placement of a nasobiliary catheter (T4); the total number of intraoperative medication additions, number of somatic motions, and number of intestinal peristalsalsis; and the number of respiratory, cardiovascular-related adverse events and anesthesia-related postoperative complications were recorded and compared. RESULTS: There was no statistically significant difference in the general information, operation time, awakening time, Ramsay sedation score, surgeon, patient satisfaction and the incidence of anesthesia-related postoperative complications among the three groups (P>0.05). Compared with the P group, the R and RP groups had lower incidence of injection pain, hypotension, bradycardia and respiratory depression, and bile heart reflex; the post-anesthesia RR and BIS values were high, and the differences were statistically significant (P<0.05). Compared with the R group, the P and RP groups had less number of somatic and intestinal motility hyperactivity, and the difference was statistically significant (P<0.05). CONCLUSION: Remimazolam combined with propofol for ERCP anesthesia can be effective, the process is smooth, and the adverse reactions are few, which is worth to promote the application in the clinic.
    Trimethylamine N-oxide: the potential target for osteoporosis treatment
    ZHAO Yangting, CHEN Chongyang, PAN Binjing, LV Xiaoyu, LIU Jingfang
    2023, 28(10):  1161-1167.  doi:10.12092/j.issn.1009-2501.2023.10.010
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    Trimethylamine N-oxide (TMAO) is an intestinal flora metabolite produced in the liver by the oxidation of trimethylamine (TMA) by hepatic enzymes. Recently, it has been found that plasma TMAO levels play an important role in the development and progression of osteoporosis. This review has presented the physiological functions and metabolic processes of TMAO, and its effects on the development and progression of osteoporosis through oxidative stress and inflammation. Plasma TMAO levels are influenced by diet as well as medications, which provides a new perspective and target for the treatment and prevention of osteoporosis.
    Research progress on the antitumor activity of costunolide
    LIU Dan, LIU Ming, JIN Liangyou, PAN Juan, XIN Haoru, LIU Mengyuan, LI Xin, ZHENG Kun, FENG Xiaoling
    2023, 28(10):  1168-1176.  doi:10.12092/j.issn.1009-2501.2023.10.011
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    In recent years, the research on the anti-tumor effect of traditional Chinese medicine has been increasing year by year. Both the effective extracted ingredients of Chinese medicine and its compound preparations have significant efficacy and advantages in tumor treatment. Costunolide, the active ingredient of Aucklandia lappa (a traditional Chinese medicine), is a natural sesquiterpene lactone, which has a variety of pharmacological effects, such as anti-oxidation, anti-inflammation, hypoglycemic effect, anti-microbial effect etc. In recent years, more and more experimental studies in vivo and in vitro have shown that this component has anti-tumor activity, which can inhibit the growth of breast cancer, gastric cancer, melanoma cancer, prostate cancer, leukemia, liver cancer, lung cancer, ovarian cancer, esophageal cancer, colorectal cancer, osteosarcoma and other tumors. Its anti-tumor mechanism mainly lies in the regulation of PI3K/AKT/mTOR, AKT-MDM 2-p53, ROS-AKT/GSK-3β, Bcr/Abl, Stat5 and other signaling pathways, which affects reactive oxygen species, apoptosis-related proteins, autophagy-related proteins, and cyclin, and thus induces apoptosis, causes autophagy and arrests cell cycle in G2/M phase, G1 phase, and S phase. In addition, the combination of costunolide with imatinib and doxorubicin can attenuate toxicity and enhance anti-tumor effect, and also reverse tumor drug resistance. By consulting and sorting out the relevant research literature at home and abroad, the author summarized the research progress of costunolide on the antitumor effect and mechanism, the combined drug use and the reversal of tumor drug resistance in order to provide theoretical basis for the development and utilization of new drugs of this ingredient.
    Pharmacological  and clinical evaluation of Dorzagliatin in the treatment of type 2 diabetes
    DU Xiaoyu, LI Yumeng, WU Huizhen, QIU Bo
    2023, 28(10):  1177-1183.  doi:10.12092/j.issn.1009-2501.2023.10.012
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    Dorzagliatin is a new dual action allosteric systemic glucokinase agonist (GKA), which can simultaneously activate the glucokinase (GK) in the pancreas and liver, promote insulin secretion and liver glycogen conversion in patients with type 2 diabetes, and improve pancreatic islets β-Cell function and insulin resistance simultaneously stimulate intestinal GK to regulate the secretion of Glucagon-like peptide-1 to play multiple hypoglycemic effects. As the first marketed GKA drug, it provides a new therapeutic approach for patients with type 2 diabetes. This article reviews the mechanism of action, pharmacokinetics, Drug interaction, clinical research and safety of Dorzagliatin.
    Research progress on the related treatment of progressive myoclonic epilepsy
    DANG Yangbin, LIANG Yuxin, WANG Tiancheng
    2023, 28(10):  1184-1194.  doi:10.12092/j.issn.1009-2501.2023.10.013
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    Progressive myoclonic epilepsy (PME) is a rare epileptic syndrome closely associated with genetic factors. The disease is primarily inherited in an autosomal recessive manner, although there are rare cases that demonstrate autosomal dominant or mitochondrial inheritance. Common clinical features include myoclonus, multiple seizure types, and progressive decline in neurological and cognitive function. PME typically manifests in late childhood or adolescence but can occur at any age. It accounts for approximately 1% of epileptic syndromes among children and adolescents worldwide. In recent years, in addition to antiseizure medications, numerous non-pharmacological treatments have emerged, including dietary therapy, neuromodulatory therapy, immunomodulatory therapy, enzyme replacement therapy, gene therapy, etc. This article aims to review the research progress in the treatment of PME.
    Progress in clinical research on remazolam
    XIN Yuqi, CAO Ya, WANG Yulong
    2023, 28(10):  1195-1200.  doi:10.12092/j.issn.1009-2501.2023.10.014
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    Benzodiazepines are among the most commonly used drugs in the field of anesthesia. Remazolam is a newly developed ultra-short-acting benzodiazepine, which has the characteristics of rapid onset, rapid recovery, high safety, and less side effects such as hypotension and respiratory depression. The aim of this review is to summarize the progress of pharmacokinetics, clinical pharmacology mechanism of action and clinical application of remazolam.
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    2023, 28(10):  1196. 
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    #br#
    2023, 28(10):  1197. 
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