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Progress in clinical application of topical anesthesia TAO Yijia, YANG Chun, LIU Cunming Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (5): 594-600.   DOI: 10.12092/j.issn.1009-2501.2023.05.015 Abstract （192）      PDF （614KB）（612）       Knowledge map    Save Topical anesthesia are being widely used in clinical diagnostic or therapeutic fields such as ophthalmology, ENT, dermatology, urology. It is defined as superficial loss of sensation in mucous membranes or skin, produced by direct application of penetrating local anesthetics. Topical anesthesia has the advantages of simple performance, high safety, quick recovery, which can effectively improve patient's satisfaction. In recent years, more and more attention has been paid to the concept of comfortable diagnosis and treatment. The new drugs and application methods of topical anesthesia are emerging constantly, special attention must be paid to their pharmacological characteristics and possible adverse reactions when using them. This article reviews the research progress of topical anesthesia in clinical application in order to provide reference for clinical practice. Related Articles | Metrics

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Model informed precision dosing: China expert consensus report JIAO Zheng, LI Xingang, SHANG Dewei, DONG Jing, ZUO Xiaocong, CHEN Bing, LIU Jianmin, PAN Yan, ZHOU Tianyan, ZHANG Jing, LIU Dongyang, LI Lujin, FANG Yi, MA Guangli, DING Junjie, ZHAO Wei, CHEN Rui, XIANG Xiaoqiang, WANG Yuzhu, GAO Jianjun, XIE Haitang, HU Pei, ZHENG Qingshan Chinese Journal of Clinical Pharmacology and Therapeutics    2021, 26 (11): 1215-1228.   DOI: 10.12092/j.issn.1009-2501.2021.11.001 Abstract （579）      PDF （1975KB）（541）       Knowledge map    Save Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China. Related Articles | Metrics

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Clinical pharmacological properties of alfentanil and its progress in anesthetic application  WANG Jinhuo, GUO Jianrong Chinese Journal of Clinical Pharmacology and Therapeutics    2021, 26 (7): 824-829.   DOI: 10.12092/j.issn.1009-2501.2021.07.015 Abstract （608）      PDF （412KB）（520）       Knowledge map    Save Alfentanil is a synthetic fentanyl derivative acting on μ opioid receptors. It is a short-acting strong analgesic.  Compared with similar anesthetic drugs such as fentanyl and sufentanil, alfentanil had the lowest titer, the fastest effect, and shorter action time. The effect reached the peak 1.4 min after intravenous injection, and the maintenance time was 10-15 min. The distribution volume was small, which was in line with the three-compartment model, and was excreted through urine after liver metabolism inactivation.  Alfentanil, one of the earliest drugs in the fentanyl family, has been widely used in analgesia, sedation, anti-anxiety, induction and maintenance of anesthesia. In recent years, the use of alfentanil has tended to be short procedure, daytime surgery, reserved breathing, and outpatient anesthesia. With the recent successful development of domestic alfentanil and its gradual application in anesthesia, alfentanil is expected to become a new choice for clinical analgesia, but its clinical application experience and related studies are very limited at present. In this paper, the pharmacological characteristics of alfentanil and its application at home and abroad were reviewed in order to provide reference for the rational clinical application of alfentanil. Related Articles | Metrics

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Pharmacological research and clinical applications progress of Lianhua Qingwen capsules/granules in respiratory diseases YIN Yujie, CHANG Liping Chinese Journal of Clinical Pharmacology and Therapeutics    2021, 26 (10): 1174-1180.   DOI: 10.12092/j.issn.1009-2501.2021.10.010 Abstract （555）      PDF （487KB）（439）       Knowledge map    Save Lianhua Qingwen capsules/granules is an innovative Chinese medicine developed under the guidance of the TCM collateral disease theory. It has the efficacy of "clearing heat and removing toxin, ventilating the lungs and discharging heat". In 2003, it was approved as a new drug by the China National Medical Products Administration, through expedited approval during/SARS, and now, it has become a representative proprietary Chinese medicine for the treatment of infectious diseases of the respiratory system. Pharmacodynamic studies have revealed that LianhuaQingwen has broad-spectrum antiviral, antibacterial and anti-inflammatory, antipyretic, cough-relieving and immunoregulation effects. Clinically it has been used in the treatment of communicable and infectious respiratory diseases such as COVID-19, influenza, upper respiratory infection, pulmonary infections, acute exacerbation of chronic obstructive pulmonary disease, etc. and has achieved remarkable curative effects. Related Articles | Metrics

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Ferroptosis regulatory signaling pathway and its research progress in related diseases ZHANG Liang, LIAO Yongqun, XIA Qinchuan, ZHOU Shitong, LI Xiaoli Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (2): 227-234.   DOI: 10.12092/j.issn.1009-2501.2022.02.015 Abstract （502）      PDF （440KB）（379）       Knowledge map    Save Ferroptosis is an iron-dependent novel type of programmed cell death. The main features of ferroptosis include lipid reactive oxygen accumulation, iron accumulation and lipid peroxidation. The main mechanisms and signal pathways of ferroptosis are complex and closely related to cystine/glutamate antiporter system, glutathione peroxidase 4, ferroptosis suppressor protein 1, and dihydroorotate dehydrogenase. This review summarizes the current regulatory mechanisms of ferroptosis and discusses the research progress of ferroptosis in tumors, non-alcoholic fatty liver disease, Parkinson's disease, and congestive heart failure. Related Articles | Metrics

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Current status of clinical drug-drug interactions research of innovative small molecule drugs in China LIU Lu, CHEN Xiaoyan Chinese Journal of Clinical Pharmacology and Therapeutics    2021, 26 (8): 863-875.   DOI: 10.12092/j.issn.1009-2501.2021.08.003 Abstract （357）      PDF （629KB）（367）       Knowledge map    Save In order to improve the efficacy or reduce the side effects, the combination of two or more drugs is often used in clinical practice, which often brings new medication problems that change the process or efficacy of a drug in vivo due to combination. This article reviews the clinical drug-drug interaction (DDI) researches of 44 novel molecular entities which were approved to be launched in China from January 2000 to March 2021. Among them, clinical DDI trials based on test drugs as substrates of the metabolic enzymes (11/44) especially as the substrates of CYP3A4 (7/11) are dominant. The results show that most of test drugs were CYP3A4 substrates with a moderate or lower sensitivity, and no highly sensitive substrates were found. The second is the clinical DDI trials based on synergy or reducing side effects, which mainly focus on the fields of tumors, diabetes, and viral infections, and these studies have not shown pharmacokinetic interactions with clinical significance. The DDI trials of test drugs as metabolic enzyme modulators account for 7/44. And transporter-based DDI trials are relatively rare and most of them are in vitro studies. With the in-depth study of drug metabolism/transport mechanisms in vivo and in vitro, especially the development of clinical trials of radioisotope-labeled drugs and computer simulations, the overall level of DDI research in China is gradually improving, which will provide a solid scientific foundation to ensure drug safety. Related Articles | Metrics

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Research strategies and considerations on non-clinical pharmacokinetics of nanomedicine FU Shujun, HUANG Fanghua, GU Jingkai, WU Wei, SUN Tao, WANG Qingli Chinese Journal of Clinical Pharmacology and Therapeutics    2021, 26 (8): 842-850.   DOI: 10.12092/j.issn.1009-2501.2021.08.001 Abstract （381）      PDF （461KB）（364）       Knowledge map    Save With the rapid development of nanotechnology, the research and development of nanomedicine has become one of the current development directions of drug innovation. The pharmacokinetic characteristics of nanomedicine are significantly different from general drugs because of the scale effect based on nanostructures, and pharmacokinetics studies of nanomedicine may be different from the general drugs. This article focuses on the research strategies and considerations on non-clinical pharmacokinetics of nanomedicine, including test agents, in vivo/in vitro assays, biological sample analysis, data evaluation and analysis etc., providing references for developers. Related Articles | Metrics

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Clinical application and research progress of remimazolam JIN Baowei, JIANG Zongming, GUO Jianrong Chinese Journal of Clinical Pharmacology and Therapeutics    2021, 26 (12): 1444-1448.   DOI: 10.12092/j.issn.1009-2501.2021.12.016 Abstract （648）      PDF （1006KB）（346）       Knowledge map    Save Remimazolam is a new ultra-short-acting sedative, with rapid onset and recovery, metabolism independent of liver and kidney function, light respiratory inhibition, stable hemodynamics, long time application without accumulation. Carboxylic acid metabolites have no pharmacological effects, and can be rapidly reversed by antagonist flumazenil, which is expected to become a new choice of clinical sedative. In this paper, pharmacological characteristics and recent research progress of remimazolam are reviewed, which can provide reference for clinical safe drug use. Related Articles | Metrics

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Research progress of α7 nicotinic acetylcholine receptors in central nervous system diseases FAN Wenxiang, ZHANG JinLu, XU Chi Chinese Journal of Clinical Pharmacology and Therapeutics    2021, 26 (9): 1065-1072.   DOI: 10.12092/j.issn.1009-2501.2021.09.013 Abstract （453）      PDF （457KB）（338）       Knowledge map    Save Alpha-7 nicotinic acetylcholine receptors (α7 nAChRs) are expressed in the central nervous system (CNS) and are thought to play a role in a wide variety of psychiatric and neurological disorders. Activation of α7 nAChR leads to an anti-inflammatory effect，which may show beneficial effects in those central nervous system disorders. In the present article, we summarize information on receptor distribution and expression, and review the effects of α7 nAChR on the CN disorders (e.g., Alzheimer's disease, Parkinson's disease, and stroke), which may provide a new idea for the development of the treatment of CNS diseases. Reference | Related Articles | Metrics

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Establishment of population pharmacokinetics model of vancomycin in patients with Neutropenia LIN Liangmo, FU Xiangjun, ZHONG Lili, WANG Hefang, WU Qiongshi, XIAO Jian Chinese Journal of Clinical Pharmacology and Therapeutics    2021, 26 (9): 1014-1022.   DOI: 10.12092/j.issn.1009-2501.2021.09.006 Abstract （253）      PDF （3687KB）（336）       Knowledge map    Save AIM: To establish a population pharmacokinetics (PPK) model of vancomycin in patients with hematological diseases who developed neutropenia.  METHODS: Patients from department of hematology with neutropenia in our hospital were taken into oue study.The patients (n=77) were performed trough and peak serum concentration of vancomycin, and their clinical data and medication information were collected. The Nonlinear mixed effect modeling approach (NONMEM) was used to establish the PPK model of those patients and model assessment and validation was carried out. Goodneess of fit plots and visual predictive check plus Bootstrap approach were used to assess validate our model. RESULTS: The model was a two compartment model, the final formulas were: clearance rate CL=6.84×(BW/70)0.75×(CLCR/116)0.895 ×exp(η1), distribution volume of central ventricle V1=20.5×(BW/70)×exp(η2), transport rate Q=15.2×(BW/70)0.75×exp(η3), distribution volume of peripheral ventricle V2=50×(BW/70)×exp(η4), (BW was body weight, CLCR was creatinine clearance rate). Additionally 15 patients with neutropenia were included to conduct external validation, and it showed good stability and accuracy. CONCLUSION: The establishment of PPK model of vancomycin in patients with hematologic diseases who developed neutropenia is helpful to realize the individualized application of vancomycin in this population. Related Articles | Metrics

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Ethical analysis and countermeasures of artificial intelligence application in clinical trials LIU Xing, LU Xiaoran, WU Ying, YU Haitao, WANG Xiaomin Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (3): 322-327.   DOI: 10.12092/j.issn.1009-2501.2022.03.012 Abstract （350）      PDF （980KB）（324）       Knowledge map    Save The development of artificial intelligence is becoming more and more mature, and has penetrated into every field of clinical trials. Artificial intelligence has brought new development opportunities for clinical trials. However, the application of artificial intelligence in clinical trials is still in the exploratory stage, facing many ethical issues, including trial risk caused by data quality, privacy protection caused by data regulation, and contradiction between data authorization and informed consent. We should precisely position the realizable application of artificial intelligence in clinical trials, understand its practical ethical issues, and formulate corresponding coping strategies to ensure the maximum improvement of the whole process performance of clinical trials, including strengthening data quality management and reducing clinical trial risks; optimizing data monitoring mechanisms to ensure data security and privacy; building a data authorization platform and improving judicial protection of informed consent, etc. Related Articles | Metrics

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PDE4 inhibitors serve as therapeutic targets for pulmonary fibrosis  LIU Nanyu, YUE Hongmei, SONG Peipei, WEI Jifang, WEI Yaqian, XIE Yingying, WANG Jiaqi Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (3): 355-360.   DOI: 10.12092/j.issn.1009-2501.2023.03.015 Abstract （276）      PDF （665KB）（322）       Knowledge map    Save Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal chronic interstitial lung disease characterized by a progressive decline in lung function, and current treatment options are limited. cAMP is one of the most important second messengers and plays a key role in relaxing airway smooth muscle cells and reducing inflammation. Phosphodiesterase (PDE) is a superfamily of enzymes, and PDE4 enzymes dominate 11 PDE super-family enzymes, available in four isoforms-PDE4A, PDE4B, PDE4C and PDE4D, which selectively decompose cAMP, while PDE4 inhibitors increase cAMP levels by preventing cAMP from breaking down, thereby exerting anti-inflammatory, anti-remodeling effects and providing an attractive drug target for the treatment of IPF. This review summarizes knowledge about the association of pulmonary fibrosis with PKE4, as well as emerging preclin-ical studies and clinical trials regarding PDE4 inhibitors. Related Articles | Metrics

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Model informed precision dosing of warfarin: China expert consensus report (2022 version) ZHANG Jinhua, LIU Maobai, CAI Mingzhi, ZHENG Yingli, LAO Haiyan, XIANG Qian, DU Liping, ZHU Zhu, DONG Jing, ZUO Xiaocong, LI Xingang, SHANG Dewei, CHEN Bing, YE Yanrong, WANG Yuzhu, GAO Jianjun, ZHANG Jian, CHEN Wansheng, XIE Haitang, JIAO Zheng Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (11): 1201-1212.   DOI: 10.12092/j.issn.1009-2501.2022.11.001 Abstract （450）      PDF （780KB）（321）       Knowledge map    Save Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin. Related Articles | Metrics

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Progress of pharmacotherapy for heart failure PENG Juan, FAN Linlin, LI Ranyi, LI Xiaoyu, LV Qianzhou, ZOU Yunzeng Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (4): 373-381.   DOI: 10.12092/j.issn.1009-2501.2022.04.004 Abstract （335）      PDF （521KB）（316）       Knowledge map    Save Heart failure is the terminal stage of all kinds of heart diseases. Despite the use of a variety of traditional drug standard treatment, the prognosis is still not ideal, and there is an urgent need for the update and improvement of new drugs and treatment methods. In recent years, angiotensin receptor-enkephalase inhibitors (Sacubitril/Valsartan), sodium-glucose cotransporter 2 inhibitors (SGLT-2i), soluble guanoside cyclase agonists (Vericiguat) and myocardial myosin activators omecamtiv mecarbil have been developed successively. SGLT2 inhibitors can improve ventricular load, reduce fibrosis and affect myocardial metabolism. sGC agonists play an anti-heart failure role by enhancing l-ARg-No-SGC-CGMP signaling pathway, improving myocardial and vascular function, reversing ventricular hypertrophy and fibrosis, slowing ventricular remodeling, and reducing ventricular afterload through systemic and pulmonary vasodilation. In addition, fineridone, a novel salt corticosteroid receptor antagonist, has also been reported in clinical studies in the field of heart failure. Therefore, it is the direction and hope for the development of heart failure in the future to select appropriate drugs for different types of patients with heart failure and carry out individualized treatment according to the optimized process of heart failure. Related Articles | Metrics

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Research progress and thinking on the metabolism of polysaccharide drugs in vivo and the key technology of PK/PD XU Hui, YANG Xinyu, ZHAO Zhehui, WANG Yan Chinese Journal of Clinical Pharmacology and Therapeutics    2021, 26 (8): 851-862.   DOI: 10.12092/j.issn.1009-2501.2021.08.002 Abstract （444）      PDF （874KB）（315）       Knowledge map    Save Polysaccharide drugs are a type of safe and effective natural drug with a wide range of pharmacological activity such as anti-tumor, immunomodulation, and oxidation, and polysaccharide drugs are currently more concerned. However, since the molecular weight of the polysaccharide is quite large, most of which do not have ultraviolet absorption and fluorescent groups, which makes the qualitative and quantitative analysis of polysaccharides are relatively difficult. In addition, endogenous sugar substances may also cause certain interference to polysaccharide assay in biological samples, and therefore, in vivo metabolism and PK/PD key technologies in polysaccharide drugs have been research hotspots. This paper summarizes the relevant literature published in recent years, reviewing the biological activity and pharmacokinetics of polysaccharide drugs, proposing gut bacteria may be potential "organ" affecting metabolism and efficacy of polysaccharide drugs, and providing thoughts on gut bacteria mediating polysaccharide drugs in vivo and key technology research of PK/PD, in order to provide more scientific ideas for pharmacokinetics, pharmacological research and molecular mechanisms of polysaccharide drugs. Related Articles | Metrics

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Research progress on drug treatment and drug resistance mechanism of gastrointestinal stromal tumors ZHAO Quanming, YANG Mandou, HU Yibo, SU Youtong, PU Li, ZHANG Yu, LI Wenliang Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (1): 82-89.   DOI: 10.12092/j.issn.1009-2501.2024.01.009 Abstract （106）      PDF （835KB）（311）       Knowledge map    Save Gastrointestinal stromal tumors (GIST) are the most common mesenchymal-derived tumors of the gastrointestinal tract. Tyrosine kinase inhibitors (TKIs) are the cornerstone of GIST therapy, but mutations in resistance genes pose many problems for treatment, especially the heterogeneity of KIT resistance mutations. In recent years, with the release of a number of GIST related drug research and experimental results, the great potential of targeted therapy, immunotherapy and combination therapy to treat GIST in different directions has been revealed, providing more therapeutic directions for GIST. This article will review the experimental research and future direction in recent years. Related Articles | Metrics

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Progress of hypertension pharmacological treatment LIU Guijian, CHENG Kuan, ZHU Wenqing, GE Junbo Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (4): 446-449.   DOI: 10.12092/j.issn.1009-2501.2022.04.015 Abstract （429）      PDF （295KB）（310）       Knowledge map    Save Hypertension is a common cardiovascular disease. Chinese guidelines for the management of hypertension, the global practice guidelines for hypertension of the International Hypertension Society (ISH) and the guidelines for the treatment of adult hypertension drugs of the World Health Organization have been issued successively, which play an important role in guiding the clinical medication of hypertension. Calcium channel blockers (CCB), angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs), angiotensin receptor neprilysin inhibitor (ARNI), thiazide diuretics and β-receptor blockers are commonly used in clinical antihypertensive drugs. The goal of hypertension drug control, the application timing of hypertension drugs, the selection of combined medication scheme, the drug selection of hypertension complicated with other diseases, and the medication of gestational hypertension are all problems that clinicians need to master. Related Articles | Metrics

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Analysis of ethical issue in the application of artificial intelligence medical devices LIU Xing, WU Ying, LI Yang, WANG Xiaomin Chinese Journal of Clinical Pharmacology and Therapeutics    2021, 26 (6): 695-699.   DOI: 10.12092/j.issn.1009-2501.2021.06.013 Abstract （436）      PDF （372KB）（300）       Knowledge map    Save With the rapid development of artificial intelligence in the medical field, artificial intelligence medical devices not only improve the efficiency of diagnosis and treatment which bring great convenience to patients, but also initiate ethical issues of medical safety, data security, algorithm bias and individual autonomy, etc. By proposing enhanced regulation and quality control, soften bias, increased transparency and improved technology as the breakthrough point, plus more respect for the autonomy of patients and doctors, this paper explored in depth the ethical issues of artificial intelligence theory and practice in hope of providing referential ideas for the regulation and supervision of artificial intelligence medical device. Related Articles | Metrics

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Bioequivalence study of buthlphthalide injection in Chinese healthy volunteers CAI Mingmin, SHAO Jing, TANG Lu, SUN Qiuyue, DOU Ting, QIAN Wei, WANG Huiping Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (1): 70-76.   DOI: 10.12092/j.issn.1009-2501.2022.01.010 Abstract （341）      PDF （1327KB）（298）       Knowledge map    Save AIM: To establish a method to investigate pharmacokinetics and bioequivalence of buthlphthalide injection. METHODS: An open, randomized, and two-cycle crossover study was conducted in 24 healthy volunteers. Plasma concentrations of buthlphthalide were determined by LC-MS/MS after administering a single dose of reference drug or test drug. Main pharmacokinetic parameters were calculated by Phoenix WinNonlin 6.4 software. RESULTS: For the test drug and the reference drug, the main pharmacokinetic parameters of flurbiprofen were as follows: AUC0-t was (541.0±78.6) ng·mL-1·h and (525.0±76.1) ng·mL-1·h, AUC0-∞ was (571.0±82.1) ng·mL-1·h and (555.0±88.1) ng·mL-1·h, Cmax was (295.0±62.7) ng/mL and (291.0±56.5) ng/mL, and the median of Tmax was 0.92 (0.33, 0.92) h and 0.92 (0.33, 0.93) h, respectively. Under two kinds of conditions, 90%CIs of AUC0-t, AUC0-∞ and Cmax of the test preparation were 80%-125% of the corresponding parameters of the reference preparation，and there was no statistical significance in Tmax between the two preparations (P＞0.05)．CONCLUSION: The test drug and the reference drug are bioequivalent． Related Articles | Metrics

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Pharmacology and clinical evaluation of vericiguat in the treatment of heart failure LIU Ping, QIU Bo, WU Huizhen Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (2): 212-218.   DOI: 10.12092/j.issn.1009-2501.2022.02.013 Abstract （740）      PDF （1896KB）（295）       Knowledge map    Save Vericiguat is a soluble guanylate cyclase stimulator, acting on nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate pathway. Vericiguat can improve the sensitivity soluble guanylate cyclase sensitivity to nitric oxide, stimulate soluble guanylate cyclase without relying on nitric oxide, leading to increased formation of cyclic guanosine monophosphate , which results in multi-dimensional protection effects for the heart. It provides a new therapeutic approach for patients with heart failure. This review provides an overview of mechanism, preclinical studies, pharmacokinetics, clinical efficacy, drug-drug interactions and limitations of vericiguat. Related Articles | Metrics

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Metabolic regulation and drug target discovery researches in China: Progress and prospect  HAO Haiping Chinese Journal of Clinical Pharmacology and Therapeutics    2021, 26 (8): 955-963.   DOI: 10.12092/j.issn.1009-2501.2021.08.009 Abstract （286）      PDF （982KB）（294）       Knowledge map    Save Metabolic regulation is an important mechanism by which organisms adapt to changes in the internal and external environment. Metabolic small molecules function as versatile messengers involved in signaling networks and organ crosstalk, which carries great implications for understanding physiological processes, revealing disease mechanisms and discovering drug targets. In this review, we present an overview of the main progresses in metabolic regulation and drug target discovery researches in China, and look forward to its future direction, which may provide a reference for the drug development endeavor based on metabolic regulation. Related Articles | Metrics

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Applications of BGUSs inhibition in tumor prevention and chemotherapy WU Rongrong, CHEN Zhiqiang, JIA Yifei, CHEN Hongqi, WANG Panpan, YAN Ru Chinese Journal of Clinical Pharmacology and Therapeutics    2021, 26 (8): 964-974.   DOI: 10.12092/j.issn.1009-2501.2021.08.010 Abstract （345）      PDF （978KB）（285）       Knowledge map    Save Bacterial β-glucuronidases (BGUSs) are an important type of hydrolase produced by gut microbiota and play an important role in tumor development and chemotherapy by deconjugating a large number of endogenous and exogenous glucuronides. In recent years, BGUSs inhibition has emerged as a promising approach to reduce cancer risk and alleviate gastrointestinal toxicity of chemotherapy drugs. However, a growing body of evidence underlines great genetic and structural diversity, functional promiscuity, and varied inhibition propensity of BGUSs, which have posed enormous challenges to identifying BGUSs involved in a specific pathophysiological or pharmacological process and developing effective inhibitors. In this review, we summarize the latest advances in structure and function of BGUSs and review the findings of BGUSs-mediated carcinogen reactivation and deconjugation of chemotherapy drugs in recent years, as well as the discovery of BGUSs inhibitors and preclinical investigation of their applications in cancer prevention and drug therapy. Finally, we discuss the prospects of BGUSs inhibition as a new strategy for tumor prevention and drug therapy. Related Articles | Metrics

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Mechanism of tyrosine kinase 2 inhibitors in treatment of plaque psoriasis and their progress in clinical trials  SHEN Jiaqing, LIU Yi Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (3): 323-330.   DOI: 10.12092/j.issn.1009-2501.2023.03.011 Abstract （188）      PDF （1286KB）（284）       Knowledge map    Save As a chronic, immune-mediated in-flammatory disease, plaque psoriasis has a great burden of disease and influences on patient's physi-cal and mental health. In the past decade, plaque psoriasis treatment with biological agents achieved breakthrough development, while oral drugs with promising efficacy and safety are yet to be met. By cell signal transduction, the Janus kinase-signal transducer and activator of transcription pathway plays an important role in numerous immune-relat-ed diseases. Tyrosine kinase 2 (TYK2), a member of the JAK family, can impact on plaque psoriasis by regulating signaling and functional responses down-stream of IL-12, IL-23, IFN. Deucravacitinib, a highly selective TYK2 inhibitor, has finished its phase 3 clinical trials and shown its efficacy and safety in treatment of plaque psoriasis. Several kinds of TYK2 inhibitors are under research and develop-ment at the moment. In this review, we demon-strate roles of JAK-STAT pathway and TYK2 in plaque psoriasis as well as updates on ongoing and recently completed trials of TYK2 inhibitors.  Related Articles | Metrics

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Research progress on immunotherapy for triple-negative breast cancer HE Lihua, ZHU Xiuzhi, JIANG Yizhou Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (8): 842-853.   DOI: 10.12092/j.issn.1009-2501.2023.08.001 Abstract （403）      PDF （754KB）（283）       Knowledge map    Save Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). It is highly aggressive, easy to relapse, and chemotherapy remains its mainstay treatment due to the lack of therapeutic targets. In recent years, many advances have been made in the development of immunotherapy for TNBC. This review summarizes the primary modalities of immunotherapy for TNBC, including immune checkpoint inhibitors, adoptive immune cell therapy, tumor vaccines and oncolytic virus. We present the latest research progress on each treatment from the perspective of clinical study and fundamental research, while introducing the potential predictive biomarkers and resistance mechanisms of immunotherapy for TNBC. Related Articles | Metrics

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Research progress of mitochondrial energy metabolism involved in the pathogenesis of depression JIN Jing, CHENG Hong Chinese Journal of Clinical Pharmacology and Therapeutics    2021, 26 (10): 1193-1199.   DOI: 10.12092/j.issn.1009-2501.2021.10.013 Abstract （251）      PDF （413KB）（283）       Knowledge map    Save Major depressive disorder (MDD) is usually an affective disorder characterized by anhedonia, cognitive decline, and social disorders. In recent years, some studies have shown that energy metabolism disorder is widespread in chronic stress models and MDD patients. Mitochondria play a central role in energy metabolism and are also involved in the regulation of oxidative stress and cell apoptosis. Thus, the abnormal changes in mitochondrial metabolism may be related to the occurrence of depression. This review summarizes the research progress of mitochondrial energy metabolism involved in the pathogenesis of depression, so as to provide reference for the research of the pathogenesis of depression and new treatment strategies based on mitochondria. Related Articles | Metrics

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Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (1): 118-.   Abstract （141）      PDF （209KB）（282）       Knowledge map    Save Related Articles | Metrics

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Effects of gut microbiota on pharmacokinetics and its consideration in the evaluation of the consistency of quality and efficacy of generic drugs ZHENG Binjie, LIU Na, ZENG Xiangchang, HUANG Xinyi, CHEN Lulu, OU-YANG Dongsheng Chinese Journal of Clinical Pharmacology and Therapeutics    2021, 26 (6): 662-671.   DOI: 10.12092/j.issn.1009-2501.2021.06.009 Abstract （305）      PDF （1454KB）（279）       Knowledge map    Save Generic drugs account for more than 95% of the chemicals market in China, and their quality is directly related to the efficacy and safety of the people. The bioequivalence evaluation with pharmacokinetic parameters as the end point is the main content of the consistency evaluation of the quality and efficacy of generic drugs. Gut microbiota is considered to have an important influence on pharmacokinetics. This article reviewed the influence of gut microbiota on pharmacokinetics and analyzed its potential significance in the evaluation of the consistency of quality and efficacy of generic drugs.  Related Articles | Metrics

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Applications of Drug Interaction Study in New Drug Development and Regulartory Decision-making SUN Bo, FU Shujun, CHEN Guiliang, LI Li Chinese Journal of Clinical Pharmacology and Therapeutics    2021, 26 (10): 1095-1102.   DOI: 10.12092/j.issn.1009-2501.2021.10.001 Abstract （310）      PDF （444KB）（273）       Knowledge map    Save Drug-drug interactions (DDI) change dose-response relationships, and may result in low efficacy or high toxicity, which are important considerations especially in medical practice with multiple-drug therapies. Predicting clinically significant drug interactions during new drug development is an important part of benefit and risk assessment in drug development and review. This article summarizes the purpose and significance of drug interactions in new drug development, the main content and precautions of DDI studies in vivo and in vitro. Drug interaction studies on novel drug approvals for 2020 in the National Medical Products Administration (NMPA) and US Food and Drug Administration (USFDA) are examined, respectively. It aims to provide reference for DDI studies and regulatory reviews in new drug development in our country. Related Articles | Metrics

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Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (9): 1077-.   Abstract （70）      PDF （224KB）（269）       Knowledge map    Save Related Articles | Metrics

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Bioequivalence trial of fasting oral sorafenib tosylate tablets in healthy Chinese subjects WU Juan, WANG Zhiqiang, ZHOU Renpeng, YANG Jingjing, QIN Huiling, ZHANG Qian, LU Chao, HU Wei Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (3): 281-286.   DOI: 10.12092/j.issn.1009-2501.2022.03.006 Abstract （349）      PDF （1247KB）（264）       Knowledge map    Save AIM: To compare the pharmacokinetic behavior of a single oral sorafenib tosylate tablets in Chinese healthy subjects under fasting conditions and evaluate the bioequivalence of the test reagent (T) and the reference reagent (R).  METHODS: A single-center, randomized, open-labeled, two-agent, three-period, three-sequence (TRR, RTR, RRT), and partially repeated crossover trial design was adopted. The trial was administered once per cycle (0.2 g) under fasting conditions. 36 healthy subjects were randomly divided into 3 groups, each with 12 cases. RESULTS: Thirty-six healthy subjects (9 females, average age 31 years) were enrolled in the trial. The upper limits of the one-sided 95% confidence interval of the pharmacokinetic parameters Cmax, AUC0-t and AUC0-∞ of the test reagent and the reference reagent after natural logarithmic transformation were －0.0908, －0.0577, －0.0541. The one-sided 95% upper limit of the confidence interval was less than 0; the ratios of the geometric mean values of the pharmacokinetic parameters Cmax, AUC0-t and AUC0-∞ of sorafenib of the test preparation and the reference preparation were 101.65%, 100.12%, and 99.24%, respectively. In the range of 80.00%-125.00%, the bioequivalence of Cmax, AUC0-t and AUC0-∞ of the test reagent and the reference reagent sorafenib was established under the fasting state. CONCLUSION: The safety and tolerability of a single oral 0.2 g sorafenib tosylate tablet by subjects under fasting conditions were good. The test reagent and the reference reagent are bioequivalent under fasting administration. Related Articles | Metrics

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Investigation of potential pharmacodynamic substances and mechanism of Qingxin-zishen prescription decoction in treatment of menopause syndrome based on HPLC-Q-TOF-MS/MS and network pharmacology YAO Qian, CHEN Yun, SHANG Juan, XI Xiaoyun, CHEN Ying, GU Xiao, JU Wenzheng, ZOU Jiandong, LU Su, XU Meijuan Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (5): 481-497.   DOI: 10.12092/j.issn.1009-2501.2022.05.001 Abstract （261）      PDF （23892KB）（259）       Knowledge map    Save AIM: To analyze the chemical ingredients of Qingxin-zishen prescription decoction (QZPD) and predict its main pharmacodynamic substances and mechanism in the prevention and treatment of menopause syndrome (MPS) with the help of high performance liquid chromatography-quadrupole-time of flight mass spectrometry (HPLC-Q-TOF/MS) combined with network pharmacology. METHODS: The chemical ingredients of QZPD were identified after analyzing the retention time, exact mass, secondary mass spectrometry fragmentation and other information obtained from HPLC-Q-TOF/MS and comparing them with the established chemical ingredients database and the literatures. The targets of ingredients in QZPD were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SwissTargetPrediction database. The disease targets of MPS were obtained through Online Mendelian Inheritance in Man (OMIM) and GeneCards Database. Gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of potential targets were analyzed with the Metascape database. Cytoscape 3.7.2 software was used to construct the network of active components-key targets-pathways. AutoDockTools 4.2.5 software was applied in the molecular docking verification between the key active components and key targets. RESULTS: A total of 83 components were identified in QZPD and 847 drug targets were predicted. After intersection them with 3 050 disease targets, 395 common targets were obtained. After network topology analysis, 74 key targets were obtained, involving mitogen-activated protein kinase (MAPK), phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt), transforming growth factor-β (TGF-β) and other signaling pathways. Molecular docking analysis results indicated that 23 key active components, such as berberine, epiberberine, coptisine, geissoschizine methyl ether, liensinine, norcoclaurine, palmatine, quercetin, and luteolin, had good binding activity with several of the key targets. CONCLUSION: This study preliminarily identifies the potential effective chemical ingredients of QZPD, predicts its targets in the prevention and treatment of MPS, which provides supporting information for the further study of the pharmacodynamic substances and mechanisms of QZPD. Related Articles | Metrics

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Pharmacokinetics of methotrexate mediated by organic anion transporter 3 in adjuvant induced arthritis rats PAN Shu, WU Yijin, ZHANG Sasa, WANG Qihai, LUO Tingting, YIN Qin Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (5): 516-525.   DOI: 10.12092/j.issn.1009-2501.2022.05.004 Abstract （196）      PDF （4176KB）（258）       Knowledge map    Save AIM: To explore the effects of inflammatory conditions on the pharmacokinetics of methotrexate (MTX) and its related mechanisms.  METHODS: The model of adjuvant induced arthritis (AIA) was established. The expression of organic anion transporter 3 (OAT3) in kidney was detected by immunohistochemistry, Western blotting and QPCR. The plasma concentration of MTX was detected by LC-MS/MS, and the pharmacokinetics of MTX after different administration time were compared by isolated rat kidney perfusion, kidney slices, in vitro cell uptake and transport experiments. RESULTS: The expression of OAT3 was significantly increased in the kidneys of AIA rats by immunohistochemistry, Western blotting and QPCR. At the same time, the concentration of MTX was detected by the optimized LC-MS/MS. The results showed that the uptake of MTX in the kidney slices of AIA rats was significantly increased, and Pro could reduce the excretion of MTX by inhibiting OAT3. Furthermore, it was demonstrated in vitro that inflammatory pathology can promote renal excretion of MTX by increasing the expression and functional activity of OAT3.CONCLUSION: Under inflammatory pathological conditions, it can increase the expression of OAT3 in the kidney, enhance its functional activity, accelerate the uptake of MTX by the kidney, and promote the excretion of MTX. Related Articles | Metrics

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Comparison of common parameter estimation methods in NONMEM 7.5.1.: A case study of ibuprofen injection in Chinese healthy adult population  LUO Mingjie, LIU Runhan, ZHOU Jie, WANG Zhenlei Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (3): 290-298.   DOI: 10.12092/j.issn.1009-2501.2023.03.007 Abstract （198）      PDF （3390KB）（256）       Knowledge map    Save NONMEM. is a software widely used in the field of population pharmacokinetics and pharmacodynamics, mainly for related data analy-sis. In theory, it mainly establishes a parameterized model, combines the obtained data, and uses dif-ferent parameter estimation methods to estimate the parameters in the model, and then analyzes the data according to the model. This paper briefly introduces the representation of parameterized models in NONMEM., and from statistical theory, summarizes three commonly used parameter esti-mation methods under the condition that the ran-domization effect parameters η and .do not inter-act. For nonlinear mixed effects models, the rela-tionships among three parameter estimation meth-ods are given under special cases of addictive intra-individual models and proportional intra-individual models. In addition, through numerical experi-ments on data of four pharmaceutical companies on the change of ibuprofen drug concentration with time, the rationality of theory is further veri-fied in terms of calculation time and model predic-tion residuals.  Related Articles | Metrics

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Progress on the pathological mechanism and treatment of frostbite  ZHANG Li, LIN Xingyao, SHANG Yun, WANG Qiang Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (3): 347-354.   DOI: 10.12092/j.issn.1009-2501.2023.03.014 Abstract （187）      PDF （808KB）（255）       Knowledge map    Save Frostbite is a tissue injury that occurs when the body is exposed to extreme cold. Its path-ological mechanism is complex and has not been ful-ly elucidated. In high cold and high altitude areas, outdoor sports people have a high risk of injury, and severe frostbite has high disability and mortality. Ex-ploring the pathological mechanism of frostbite is helpful to determine the treatment methods and timing. At present, the clinical treatment of frostbite is mainly symptomatic treatment, such as drug treatment and surgical treatment, but the curative effect can not meet the clinical needs. Therefore, it is of great significance to seek more efficient drugs or treatment methods. This article reviews the rele-vant research progress in pathophysiological mecha-nism, clinical treatment, cellular and molecular path-ways of frostbite in recent years, in order to provide new ideas for future research and clinical treatment.  Related Articles | Metrics

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Molecular mechanism and treatment of pulmonary fibrosis ZHOU Shiqin, LUO Yali, ZHOU Wen, Qi Xiaofeng, XIAO Mengyong Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (10): 1133-1147.   DOI: 10.12092/j.issn.1009-2501.2022.10.008 Abstract （204）      PDF （2959KB）（254）       Knowledge map    Save Pulmonary fibrosis (PF) is a chronic progressive interstitial lung disease. The pathogenesis of PF is not yet clear. The two anti fibrosis drugs approved for IPF treatment, nidanib and pirfenidone, have been proved to reduce the decline of pulmonary function of PF, but both have side effects. So far, there is no obvious and effective treatment to prevent the progress of PF. Therefore, this review focuses on the different cells, molecular mechanisms involved in PF and the current treatment progress of PF, so as to provide theoretical support for a better understanding of these cells, molecular mechanisms and drug development and application in PF. Related Articles | Metrics

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Potential health benefits of resveratrol: a pharmacokinetics-caused conundrum WANG Yaya, CHU Zixuan, YANG Junling, Olajide E. Olaleye, HE Rongrong, LI Muzi, CHENG Chen, LI Chuan Chinese Journal of Clinical Pharmacology and Therapeutics    2021, 26 (8): 931-954.   DOI: 10.12092/j.issn.1009-2501.2021.08.008 Abstract （325）      PDF （2366KB）（254）       Knowledge map    Save Resveratrol (3,5,4'-trihydroxy-trans-stilbene) was first identified from white hellebore (Veratrum grandiflorum) root and began to attract interest when its presence in red wine and cardiovascular activities were reported, leading to speculation of its contribution to the 'French paradox'. Besides the cardiovascular protection, potential health benefits of resveratrol include calorie restriction-like effects, cancer prevention and adjunctive therapy, and neuroprotection. In order to achieve translational applications of these potential benefits, pharmacokinetic research was performed for plasma pharmacokinetics and related disposition of orally dosed resveratrol. This paper summarizes the known human pharmacokinetic characteristics of resveratrol after oral administration and various attempts to improve its systemic exposure level from the perspectives of systemic exposure and in vivo process. However, available pharmacokinetic data of resveratrol has raised conundrums that limit translating potential benefits to clinics: (1) differences between the unchanged resveratrol used in bioactivity studies and its major circulating forms (i.e., metabolites) after dosing; (2) resveratrol's test concentrations used to exert in vitro bioactivities related to the benefits significantly higher than the compound's clinically achievable concentrations; (3) resveratrol's concentrations achievable (estimated from the pharmacokinetics) from doses used to produce in vivo efficacy significantly lower than the effective concentrations found in studies of related action mechanism (suggesting unreliability of test mechanism). In the last part of this review, we provide recommendations for future pharmacokinetic investigations of resveratrol, including a more systematic investigation of systemic exposure to resveratrol metabolites, their access to in vivo loci responsible for the benefits, and their disposition in target cells; an investigation of colon-luminal exposure to resveratrol and its metabolites for accessing colonic microbiota; and a multi-compound pharmacokinetic investigation of red wine.  Related Articles | Metrics

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Disease progression model for Alzheimer's disease and its research progress ZHANG Ningyuan, ZHENG Xijun, XU Ling, LIU Hongxia, ZHENG Qingshan Chinese Journal of Clinical Pharmacology and Therapeutics    2021, 26 (6): 687-694.   DOI: 10.12092/j.issn.1009-2501.2021.06.012 Abstract （404）      PDF （681KB）（253）       Knowledge map    Save Alzheimer's disease (AD) is a degenerative neurological disease with unclear pathogenesis. The disease progress/trajectory of AD patients can be adequately described by establishing quantitative pharmacological disease progression model. Integrating biomarker information into the model can provide more insight to understand the potential pathological mechanisms and facilitate the optimization of future trial design. Several empirical and semi-mechanism disease progression models have been published. This mini-review is expected to offer some references for the further AD clinical research and new drug development. Related Articles | Metrics

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Research progress of lactate dehydrogenase A in digestive system tumors and related drugs WANG Siyu, LI Jiawei, LI Chenghao, LI Ling, GUO Qingyang, QIU Lu, ZHOU Shiqin, LIU Yongqi Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (4): 445-454.   DOI: 10.12092/j.issn.1009-2501.2023.04.012 Abstract （184）      PDF （1441KB）（253）       Knowledge map    Save Malignant tumors of digestive system are highly prevalent malignant tumors that seriously threaten human health around the world. At present, the curative efficacy and prognosis of traditional treatment methods cannot reach the expectation, so it is urgent to find new targets for cancer treatment and realize targeted therapy for tumors. Abnormal energy metabolism in tumor  cells is regarded as a hallmark of cancer, and malignant tumor cells absorb glucose through aerobic glycolysis pathway, and obtain a small amount of energy and produce lactate under the catalysis of a series of enzymes. Lactate dehydrogenase A (Lactate dehydrogenase A, LDHA), as a key enzyme in the aerobic glycolysis pathway of tumor cells, plays an important role in the metabolic changes of tumor cells. Studies have demonstrated that LDHA has high expression characteristics in a variety of tumor cells,and its high expression in clinic is often related to the poor prognosis and high metastasis rate of tumors, which is expected to be a new target for cancer therapy. This article reviews the role of LDHA in the development of digestive system tu- mors and the research progress of related drugs. Related Articles | Metrics

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Application of quantitative pharmacology in vaccine research and de-velopment: overview and prospect  MA Guangli, ZHANG Jing Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (3): 315-322.   DOI: 10.12092/j.issn.1009-2501.2023.03.010 Abstract （190）      PDF （1748KB）（251）       Knowledge map    Save This article introduces the mechanism including antigen presentation, adjuvant, lymphatic system and the characteristics of vaccine, and then summarizes the key applications of core pharmaco-metrics approaches including QSP, PK/PD, dose re-sponse analysis, MBMA, in dose-response, preclini-cal and clinical translation, and correlation be-tween biomarkers and efficacy of vaccines. It is ex-pected that the successful application of model in-formed drug development can promote model in-formed vaccine development so that pharmaco-metrics makes its due contributions to the develop-ment of safer, more effective and more controlla-ble vaccine products. Related Articles | Metrics

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Research progress on antipyretic effect of Chinese medicine CHEN Shengfu, LI Xiaolin, WANG Weigang, DU Weize, LI Maoxing Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (3): 334-344.   DOI: 10.12092/j.issn.1009-2501.2022.03.014 Abstract （291）      PDF （915KB）（250）       Knowledge map    Save Fever is a sign of infection and inflammatory diseases in the body. Persistent high fever will lead to cell degeneration, causing multiple organ dysfunction, and seriously affecting brain nerve and tissue function. Although the fever process is common and ordinary, its pathological mechanism involves multiple signaling pathways, such as nuclear transcription factor κB signaling pathway, Toll-like receptor 4 signaling pathway. A large number of studies have shown that traditional Chinese medicine compound and its active components can reduce serum inflammatory factors (TNF-α, IL-1β and IL-6) and hypothalamic thermoregulatory mediators (PGE2, cAMP), inhibit NF-κB signaling pathway, and effectively inhibit the pathological increase of body temperature. This paper summarizes the relevant literature in PubMed and CNKI database, and systematically expounds the active components of traditional Chinese medicine and the antipyretic effect of compound prescription, in order to provide theoretical basis and research ideas for the use of traditional Chinese medicine in the treatment of fever and the excavation of new anti-fever drugs. Related Articles | Metrics