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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 （867）      PDF （1006KB）（425）       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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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 （845）      PDF （1896KB）（368）       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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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 （820）      PDF （440KB）（566）       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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Research progress in pharmacological and non-pharmacological treatments of hypertension XU Jianfei, LIN Li Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (4): 433-441.   DOI: 10.12092/j.issn.1009-2501.2022.04.013 Abstract （739）      PDF （473KB）（351）       Knowledge map    Save Hypertension is the most common chronic non-communicable disease in the world and the most important risk factor for cardiovascular and cerebrovascular diseases. At present, the control rate of hypertension treatment standard is less than 50%, and it is still not effectively managed to a large extent. Despite numerous clinical studies and trials over the past four decades, the progress of new antihypertensive drugs has not been satisfactory. This review discusses recent advances in pharmacological and non-pharmacological treatments for patients with hypertension, and may provide new options for clinical hypertension treatment in the future. 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 （727）      PDF （1975KB）（621）       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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Human body networks mechanisms of melatonin and its clinical applications SHAO Mingkun, LIU Rong, SUN Pin, GUAN Shui, LIAO Bingcan, LI Sha, CONG Tao, LIANG Kai, MA Hui, SUN Changkai Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (9): 1031-1040.   DOI: 10.12092/j.issn.1009-2501.2022.09.010 Abstract （704）      PDF （2524KB）（324）       Knowledge map    Save Melatonin is mainly an endogenous indoleamine hormone with many physiological functions. Melatonin not only plays an important role in the treatment of sleep disorders, but also plays an important role in the treatment of nervous system diseases, cancer, cardiovascular diseases, and bone diseases. In this paper, the human body networks mechanisms and the clinical applications of melatonin were summarized to provide reference for exploring the focus and direction of further clinical application research. Related Articles | Metrics

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Regulatory mechanism of LDLR and research progress of its related diseases and drugs LI Miao, YU Qinwei, JIANG Zhenzhou, ZHANG Luyong, Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (8): 946-954.   DOI: 10.12092/j.issn.1009-2501.2022.08.014 Abstract （663）      PDF （519KB）（333）       Knowledge map    Save Cholesterol is an important lipid component in the body, which not only participates in the formation of cell membranes, but also is the raw material for the synthesis of bile acids and steroid hormones. Low density lipoprotein receptor (LDLR) is involved in cholesterol metabolism and plays an important role in maintaining the cholesterol homeostasis of organism cells. The expression of LDLR is precisely regulated by transcription, post-transcription and post-translation, and the imbalance of ldlr expression will lead to the occurrence and development of many diseases. In this paper, the molecular regulation mechanism of LDLR, the damage of target organs caused by the imbalance of LDLR expression and the research and development progress of drugs targeting LDLR are reviewed, which provides theoretical basis for further understanding of the progress of diseases related to lipid metabolism disorder and new insights for developing drugs targeting LDLR with more effective and less side effects. 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 （644）      PDF （754KB）（410）       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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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 （634）      PDF （487KB）（637）       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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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 （621）      PDF （295KB）（384）       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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Role of the m7G methyltransferase METTL1 in tumours HONG Ziqiang, GOU Wenxi, CUI Baiqiang, BAI Xiangdou, JIN Dacheng, GOU Yunjiu Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (1): 93-100.   DOI: 10.12092/j.issn.1009-2501.2023.01.012 Abstract （601）      PDF （1346KB）（205）       Knowledge map    Save N7-methylguanosine (m7G) is a common post-transcriptional modification of RNA that plays an important role in RNA processing, metabolism and function and is mainly regulated by the methyltransferase 1 (METTL1) and WD repeat domain 4 (WDR4) complexes. Several studies have shown that the METTL1/WDR4 complex promotes or inhibits the progression of many tumours, including head and neck tumours, lung, liver, colon, bladder and esophageal squamous cancers, which are dependent on m7G methylation modification of tRNA or miRNA. Therefore, METTL1 and m7G modification can be used as biomarkers or potential intervention targets, providing a new direction for early diagnosis and treatment of tumors. This article will mainly discuss the mechanism and corresponding research progress of METTL1 in tumorigenesis through m7G. Related Articles | Metrics

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Research progress of β2 microglobulin ZHANG Xiaoyi, KUAI Zheng, ZOU Yunzeng Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (4): 390-396.   DOI: 10.12092/j.issn.1009-2501.2022.04.006 Abstract （588）      PDF （411KB）（212）       Knowledge map    Save β2 microglobulin (β2-MG) is a key component I molecule of the major histocompatibility complex class that assists in the cytotoxic T lymphocyte (CTL) immune response. Serum β2-MG content is dynamically correlated with many diseases. Most studies on β2-MG mainly focus on the pathogenesis of kidney disease, tumor and amyloid fibrils. In recent years, some studies have found that β2-MG is also involved in the adverse prognosis of cardiovascular system, cognitive impairment of aging and antibacterial effects. This paper summarized the domestic and foreign studies on β2-MG in recent years, and proposed the possible role of β2-MG in multi-system human body and its potential application prospect of drug molecular targeting. 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 （548）      PDF （780KB）（413）       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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Advances in the study of iodine-resistant differentiated thyroid cancer CHEN Wenjie, WANG Yabing, CHEN Xiaolin, REN Junling, ZHAO Wanjun, CHEN bin Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (1): 116-120.   DOI: 10.12092/j.issn.1009-2501.2022.01.016 Abstract （540）      PDF （358KB）（252）       Knowledge map    Save Thyroid cancer is one of the most common malignant tumors. After standardized surgery, selective 131I radiotherapy and gonadotropin suppression therapy, the overall prognosis of most patients with differentiated thyroid cancer is good. However, there are still a small number of patients who are not sensitive to radioactive iodine treatment and have mutations of one or more oncogenes, which become iodine-resistant differentiated thyroid cancer. The application of traditional treatment methods cannot achieve satisfactory efficacy, the disease progresses rapidly and the mortality rate is high. This article reviews the progress in the diagnosis and treatment of iodine-resistant differentiated thyroid cancer in order to obtain the necessary time for early identification and targeted therapy. Related Articles | Metrics

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Progress of medical treatment of coronary heart disease CHANG Shufu Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (4): 405-408.   DOI: 10.12092/j.issn.1009-2501.2022.04.008 Abstract （532）      PDF （298KB）（332）       Knowledge map    Save Coronary heart disease (CHD) treatment methods are changing rapidly, and new drugs are constantly entering the clinic. Antiplatelet drugs are the basis for the treatment of CHD, but there are currently no new drugs that can challenge the status of aspirin and P2Y12 receptor inhibitors. Inflammation is the mechanism of the occurrence and development of CHD, and anti-inflammatory treatment is just beginning, and further exploration is still needed. This paper aims to summarize the progress of drug treatment for CHD and provide a new perspective for clinical practice. Related Articles | Metrics

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New progress in research and application of fenneridone CHENG Kuan Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (4): 450-456.   DOI: 10.12092/j.issn.1009-2501.2022.04.016 Abstract （532）      PDF （410KB）（298）       Knowledge map    Save Aldosterone is a mineralocorticoid hormone produced by the adrenal cortex, which acts on receptors in the distal and collecting tubules of the nephron, causing reabsorption of sodium and secretion of potassium. Aldosterone can promote inflammatory response and lead to myocardial remodeling and fibrosis. Aldosterone acts through mineralocorticoid receptor (MR), which is mainly expressed in heart, kidney and blood vessels. Excessive activation of MR can cause endothelial dysfunction, fibrinolysis disorder, oxidative stress, cardiovascular and renal fibrosis, and eventually lead to organ injury, dysfunction and even organ failure. Mineralocorticoid receptor antagonist (MRA) can achieve cardiorenal protection by inhibiting inflammation and fibrosis caused by MR activation. The novel nonsteroidal MRA fenneridone can effectively block MR with its high selectivity and bring definite cardiac and renal protective effects. Related Articles | Metrics

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Advances in targeted therapy for HER2-positive breast cancer LUO Shiping, ZHANG Jie, YU Yushuai, SONG Chuangui Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (8): 876-886.   DOI: 10.12092/j.issn.1009-2501.2023.08.004 Abstract （525）      PDF （761KB）（228）       Knowledge map    Save Since the beginning of the 21st century, with the continuous development of anti-HER2-targeted drugs, more treatment options have been provided for patients with HER2-positive breast cancer and the survival prognosis has been significantly improved. At present, anti-HER2 targeted drugs mainly include monoclonal antibody drugs such as trastuzumab and pertuzumab, small molecule tyrosine kinase inhibitors such as lapatinib and neratinib, and antibody-drug conjugates such as T-DM1 and T-DXd, which play an extremely important role in different disease processes. The treatment of HER2-positive breast cancer is based on targeted therapy with trastuzumab. Early-stage patients with high risk factors can be treated with intensive targeted therapy to further improve the prognosis, while advanced patients need a reasonable arrangement of targeted therapy to overcome drug resistance and prolong survival. This article will review the current status, the latest research progress and the future prospects of anti-HER2 targeted therapy in different stages of the disease. Related Articles | Metrics

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New development of lipid-lowering therapy of coronary heart disease: Bempedoic acid WANG Qi, ZOU Yunzeng Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (4): 369-372.   DOI: 10.12092/j.issn.1009-2501.2022.04.003 Abstract （510）      PDF （273KB）（176）       Knowledge map    Save Inability to tolerate statins because of muscle symptoms contributes to uncontrolled cholesterol levels and insufficient cardiovascular risk reduction. Bempedoic acid, an enzyme with high expression in the liver but that is undetectable in the skeletal muscle. Lack of the activating enzyme in skeletal muscle may prevent the muscular adverse effects associated with statins. In this review, we summarize the latest advances in bempedoic acid, and review the phase 2 and phase 3 clinical trials results, adverse events, and the clinical trials results in progress of Bempedoic acid. Finally, we discuss the current status of bempedoic acid in the clinical works.  Related Articles | Metrics

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Integrins targeting αv are used as drug 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    2022, 27 (6): 709-714.   DOI: 10.12092/j.issn.1009-2501.2022.06.015 Abstract （481）      PDF （369KB）（216）       Knowledge map    Save IPF is a chronic progressive interstitial lung disease of unknown etiology and poor prognosis, and despite receive treatment, most patients consideration are likely to progress or worsen. Integrins are heterodimer cell surface proteins that are promising therapeutic targets for intervention in pulmonary fibrosis. Alphav integrins are central to the development of fibrosis because they activate latent TGF-β, a known pro-fibrosis cytokine. The alphav subunit may form heterodimers with the β1, β3, β5, β6, or β8 subunits, one or more of which are essential for the development of pulmonary fibrosis, but their relative importance is unclear. This review summarizes the knowledge of the association of pulmonary fibrosis with alpha-val-integrins, as well as emerging preclinical studies and clinical trials of alpha-fibrosis inhibitors. Related Articles | Metrics

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Bioequivalence study of cinacalcet hydrochloride tablets in healthy Chinese volunteers YAN Qiangyong, XIANG Daxiong, ZHU Ronghua, YANG Lingfeng, YANG Xiding, LI Jingjing, FAN Xiao, LIU Sai, XIONG Shoujun, FANG Pingfei Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (2): 171-177.   DOI: 10.12092/j.issn.1009-2501.2023.02.007 Abstract （469）      PDF （1053KB）（155）       Knowledge map    Save AIM: To evaluate the bioequivalence of cinacalcet hydrochloride tablets in healthy Chinese volunteers. METHODS: A randomized, open, double-period and crossover trial was conducted, 48 healthy volunteers were administered a single dose of cinacalcet test tablets or reference tablets orally under each fasting and fed condition. The concentration of cinacalcet was determined by validated LC-MS/MS method. Pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.0 to study its bioequivalence. RESULTS: The main pharmacokinetic parameters of test tablets and reference tablets under fasting condition were as follows: Cmax (5.96±4.15) and (6.11±4.08) ng/mL, AUC0-72h (45.82±30.20) and (46.11±29.50) ng·h·mL-1, AUC0-∞  (49.65±33.64) and (49.63±32.01) ng·h·mL-1, Tmax (4.5［1.0, 6.0］) and (4.5［1.0, 6.0］) h, t1/2 (23.15±9.23) and (22.43±8.81) h, respectively. Under fed condition, the main pharmacokinetic parameters of test tablets and reference tablets were as follows: Cmax (11.14±5.24) and  (10.24±5.39) ng/mL, AUC0-72h (76.70±39.34) and (75.18±34.36) ng·h·mL-1, AUC0-∞ (83.28±43.00) and (81.38±38.03) ng·h·mL-1, Tmax (3.0［1.5,5.0］) and (4.3［1.5,7.0］) h, t1/2 (28.07±6.37) and (27.46±5.44) h, respectively. The 90%confidence intervals of the geometric average ratios of Cmax, AUC0-72h and AUC0-∞ were all within the equivalent interval of 80.00%-125.00%. CONCLUSION: Two formulations of cinacalcet tablets are bioequivalent and safe. 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 （464）      PDF （665KB）（489）       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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Recent progress of mitophagy in hepatic insulin resistance QUAN Haiyan, JIANG Xing, HE Lu Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (2): 198-204.   DOI: 10.12092/j.issn.1009-2501.2022.02.011 Abstract （448）      PDF （392KB）（198）       Knowledge map    Save Metabolic syndrome, characterized by centralobesity, hypertension, bycentralobesity, hypertension, and hyperlipidemia, increases the incidence and mortality of cardiovascular disease, type 2 diabetes, nonalcoholic fatty liver disease, and other metabolic diseases. It is well known that insulin resistance, especially hepatic insulin resistance, is a risk factor for metabolic syndrome. Current research has shown that the accumulation of hepatic fatty acid can cause hepatic insulin resistance through increased gluconeogenesis, lipogenesis, chronic inflammation, oxidative stress and endoplasmic reticulum stress, and impaired insulin signal pathway. Mitochondria are the major sites of fatty acid β-oxidation, which is the major degradation mechanism of fatty acids. Mitochondrial dysfunction has been shown to be involved in the development of hepatic fatty acid-induced hepatic insulin resistance. Mitochondrial autophagy (mitophagy), a catabolic process, selectively degrades damaged mitochondria to reverse mitochondrial dysfunction and preserve mitochondrial dynamics and function. Therefore, mitophagy can promote mitochondrial fatty acid oxidation to inhibit hepatic fatty acid accumulation and improve hepatic insulin resistance. Here, we review advances in our understanding of the relationship between mitophagy and hepatic insulin resistance. Additionally, we also highlight the potential value of mitophagy in the treatment of hepatic insulin resistance and metabolic syndrome. Related Articles | Metrics

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New narcotic analgesics: esketamine JIA Tao, TENG Jinliang Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (7): 834-840.   DOI: 10.12092/j.issn.1009-2501.2022.07.015 Abstract （442）      PDF （468KB）（280）       Knowledge map    Save Esketamine is an excellent anesthetic with higher potency than ketamine, fast onset of action, rapid elimination from the body, mild respiratory depression, and little impact on the circulatory system. It has unique advantages in the field of clinical anesthesia and analgesia. Its sub-anesthetic dose regimen is the most widely used in various surgeries and short examinations. Compared with traditional ketamine, the dose required for anesthesia effect and mental side effects are lower, and the analgesic effect is stronger. It has great clinical application prospects. 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 （441）      PDF （1327KB）（366）       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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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 （440）      PDF （444KB）（314）       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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Research progress in population pharmacokinetics of rituximab LI Mengxue, HE Jie, YU Xiaxia, HU Linlin, SHAO Hua Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (4): 468-474.   DOI: 10.12092/j.issn.1009-2501.2023.04.015 Abstract （438）      PDF （638KB）（351）       Knowledge map    Save Rituximab, a chimeric human-mouse monoclonal antibody, has been used as a first-line treatment for CD20+ B-cell non-Hodgkin lymphoma in combination with chemotherapy. It is also used for autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus and immunemediated nephropathy. The clinical therapeutic effect of rituximab is significant. However, individual pharmacokinetics vary greatly, which bring some uncertainties to the efficacy and safety of clinical application, individualized treatment is needed to improve the rationality of its medication. Currently, studies on the optimization of rituximab administration regimen using population pharmacokinetics have been reported. Our paper reviewed the research progress in population pharmacokinetics of rituximab, aiming to provide reference to formulate an individualized dosing scheme of rituximab and realize precise administration for domestic patients. Related Articles | Metrics

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Application of β-blockers for hypertension CUI Sumei, CUI Zhaoqiang Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (4): 423-427.   DOI: 10.12092/j.issn.1009-2501.2022.04.011 Abstract （436）      PDF （325KB）（240）       Knowledge map    Save β-blockers are widely administered to patients with various cardiovascular diseases including hypertension. However, in recent years, studies have questioned or even denied the antihypertensive effect of β-blockers, which has caused confusion to cardiovascular clinicians. Based on the systematic analysis of a number of studies, the author believes that β-blockers still remain the status as the first-line antihypertensives. Related Articles | Metrics

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Current opinions and developments of non-pharmacological treatments of hypertension based on sympathetic nervous system YE Peng, TAN Xing, LENG Yueqi, WANG Yangkai, WANG Weizhong Chinese Journal of Clinical Pharmacology and Therapeutics    2021, 26 (12): 1335-1343.   DOI: 10.12092/j.issn.1009-2501.2021.12.001 Abstract （433）      PDF （1862KB）（284）       Knowledge map    Save Hypertension is a serious disease that endangers human health. Although the clinical efficiency of anti-hypertensive drugs have achieved good results, there are still many different types of resistant hypertension such as drug tolerance, and the incidence of complications of hypertension such as heart failure and stroke is still high. Therefore, the development and application of non-pharmacological treatment strategies have become an important aspect of the treatment of hypertension. The sympathetic nervous system plays a key role in the pathogenesis of hypertension. At present, most non-pharmacological treatment technologies for the prevention and treatment of hypertension mainly target the sympathetic nerve function. These technologies mainly include deep brain stimulation and renal denervation. Central iliac arteriovenous anastomosis, baroreflex activation therapy, endovascular baroreflex amplification, carotid body ablation, etc. This review focuses on the application status and related advantages and disadvantages of the above-mentioned non-pharmacological treatment methods based on the sympathetic nervous system, and provides new ideas and multiple options for treatment of hypertension. Related Articles | Metrics

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Effects of sakubatril valsartan combined with dagliflozin in the treatment of patients with HFrEF and the effect on serum cTnⅠ and BNP levels YANG Sheng, WANG Deguo Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (9): 1010-1015.   DOI: 10.12092/j.issn.1009-2501.2022.09.008 Abstract （427）      PDF （424KB）（139）       Knowledge map    Save AIM: To investigate the effect of sakubatril valsartan combined with dagliflozin in the treatment of patients with HFrEF and the effect on serum cardiac troponin I (CTnI) and B-type brain natriuretic peptide (BNP) levels.  METHODS: Seventy patients with HFrEF admitted to our hospital from January 2020 to October 2021 were selected and divided, using random number table method, into control group (35 cases, conventional treatment + sakubatril valsartan) and observation group (35 cases, conventional treatment + sakubatril valsartan + dagliflozin). The treatment effect, myocardial markers (serum cTnI, BNP), exercise capacity ( 6 min walking experiment), myocardial remodeling-related indexes ［(left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic internal diameter (LVESD), left ventricular ejection fraction (LVEF)］ and adverse effects were compared between the two groups. RESULTS: The total effective rate of treatment in the observation group was lower than that in the control group (P<0.05), and the difference was not statistically significant (P>0.05); the changing trends of serum BNP and cTnI expressions were the same in the two groups at 3 months and 6 months of treatment, and the serum BNP and cTnI expressions of patients in the observation group were lower than those in the control group (P<0.05); at the end of treatment, the 6 min walk test results of patients in the observation group were better than those in the control group (P<0.05); At the end of treatment, the LVEDd and LVESD values in the observation group were lower than those in the control group, and the LVEF values were higher than those in the control group (P<0.05); the differences were not statistically significant when comparing the total incidence of adverse reactions between the two groups (P>0.05). CONCLUSION: The combination of sakubatril valsartan and dagliflozin is effective for patients with HFrEF, and can effectively regulate serum cTnI and BNP levels with low adverse reactions. Related Articles | Metrics

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Advances in new fast-acting antidepressants YU Zefang, FAN Liju, YIN Xiaoyu, GAO Lili, DONG Zhanjun Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (5): 595-600.   DOI: 10.12092/j.issn.1009-2501.2022.05.013 Abstract （422）      PDF （384KB）（250）       Knowledge map    Save Antidepressants are mainly used to treat mental illnesses. Traditional antidepressants mainly target monoamine neurotransmitters, but these drugs are slow to be effective and cannot meet clinical needs. Recently, therapeutics have been developed that depart from the traditional monoamine hypothesis and focus on the glutamatergic, GABAergic, opioidergic, and inflammatory systems. In recent years, great progress has been made in the development of new antidepressants, some of which have been applied in clinical practice. This article mainly summarizes the research mechanisms and treatment programs of new antidepressants, and briefly reviews common rapid-acting antidepressants. Related Articles | Metrics

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Population pharmacokinetics/pharmacodynamics of tigecycline in the treatment of different infectious diseases LI Wenchao, BAI Xiangrong, LI Xiaoling, JIANG Dechun Chinese Journal of Clinical Pharmacology and Therapeutics    2021, 26 (11): 1265-1272.   DOI: 10.12092/j.issn.1009-2501.2021.11.007 Abstract （422）      PDF （649KB）（241）       Knowledge map    Save AIM: To provide reference for the clinical application of tigecycline and subsequent population pharmacokinetic-pharmacodynamics study in the future. METHODS: The Chinese and English keywords of "Tigecycline", "population pharmacokinetics", "population pharmacokinetic model", "pharmacodynamics" or "Tigecycline" pharmacokinetics "were used to search the relevant references published from the time of self-establishment to June 1, 2021 in PubMed, China Knowledge Infrastructure, Wanfang and other databases. The research progress of population pharmacokinetics and pharmacodynamics of tigecycline was reviewed. RESULTS & CONCLUSION: A total of 73 relevant references were retrieved, including 8 tigecycline PPK studies and 7 tigecycline PK/PD studies. At present, tigecycline PPK models had been established in patients with complex intra-abdominal infections, skin and skin and soft tissue infections, community-acquired pneumonia, nosocomial pneumonia, septic shock and other severe infections, including 8 two-compartment models. The main covariates affecting tigecycline plasma clearance were weight-related, liver function and renal function-related parameters. Body weight was also an important factor influencing the apparent volume of distribution. The effect of different disease types on the pharmacokinetics of tigecycline was different, and it needed to be considered and selected in combination with the specific circumstances of patients when formulating clinical dosing regimens. Pharmacodynamics studies should consider not only the type of disease, pathogens and patient factors themselves, but also the characteristics of atypical nonlinear plasma protein binding of tigecycline. In order to accurately understand the efficacy of different dose regimens, it was necessary to monitor the therapeutic drugs of tigecycline. Related Articles | Metrics

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Effects of different postpartum withdrawal time of tenofovir on hepatitis B virus markers, virology and biochemical indexes TAO Chengjing, LIU Shourong, CHENG Xiaoxian, HU Jiannv, BAI Xiuli, ZHANG Suying, ZHAO Chun, ZUO Zhongbao Chinese Journal of Clinical Pharmacology and Therapeutics    2021, 26 (10): 1146-1152.   DOI: 10.12092/j.issn.1009-2501.2021.10.006 Abstract （421）      PDF （709KB）（175）       Knowledge map    Save AIM: To evaluate the effect of TDF withdrawal time on changes of serum HBV-M, HBV DNA and ALT level in the mother-to-child blocking of the maternal population. METHODS: A prospective, randomized and controlled study was conducted. The 120 pregnant women with HBV who took TDF during 24 to 28 weeks of gestation were randomly divided into group A (withdrawal at delivery) and group B (withdrawal at 4 weeks postpartum), levels of HBV-M,HBV DNA, and ALT at different times were detected. The results were statistically analyzed by Wilcoxon Rank-sum test and χ2 test. RESULTS: In total, 106 pregnant women have completed testing and follow-up, including 56 in group A and 50 in group B. The levels of HBsAg showed no significant difference in both groups and between the two groups (P>0.05). The levels of HBeAg (M=2.920Log10S/CO) and HBV DNA (M=1.477Log10copies/mL) of group B at withdrawal were significantly lower than group A (M=3.045Log10S/CO, M=2.647Log10 copies/mL). The difference were statistically significant (Z=3.126, P=0.002; Z=－2.940, P＜0.001). The HBeAg serological conversional rate of group B was 22.00%(11/50), which was higher than group A ［8.93% (5/56)］, but it was not statistically significant (P>0.05). The ALT abnormal incidence rate after withdrawal (41.07% in group A and 40.00% in group B) were significantly higher than during pregnancy (19.64% in group A, 16.00% in group B). The difference were statistically significant (group A: χ2=6.081, P=0.014; group B: χ2=7.143, P=0.008); The result of group A and group B compared each was no statistics significant (χ2=0.238, P=0.625). About women with abnormal ALT during pregnancy, the abnormal incidence rate of ALT in group A after withdrawal (100%) was significantly higher than in group B (62.50%) , and the difference was statistically significant (Z=0.696, P=0.048). CONCLUSION: The levels of HBsAg, HBeAg, HBV DNA and ALT have no difference between group A (withdrawal at delivery) and group B(withdrawal at 4 weeks after delivery). About women with abnormal ALT during pregnancy, people in group A show more incurrence than group B after drug withdrawal. Pregnant women with abnormal ALT during pregnancy should enhance postpartum monitoring and delay the drug time when necessary. 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 （420）      PDF （980KB）（364）       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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Analysis of the clinical efficacy of three kinds of Chinese patent medicines assisting tacrolimus in the treatment of nephrotic syndrome ZHONG Lingjun, HU Linlin, HE Jie, SHAO Hua Chinese Journal of Clinical Pharmacology and Therapeutics    2021, 26 (11): 1285-1291.   DOI: 10.12092/j.issn.1009-2501.2021.11.010 Abstract （418）      PDF （425KB）（135）       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 （417）      PDF （1247KB）（301）       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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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 （417）      PDF （521KB）（381）       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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Design and evaluation of clinical trials of COVID-19 vaccine and monoclonal neutralizing antibody LI Shanshan, GU Jingwen, ZHANG Jing, YANG Haijing, LIU Wei, YU Yiqi, ZHANG Wenhong Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (2): 190-197.   DOI: 10.12092/j.issn.1009-2501.2022.02.010 Abstract （412）      PDF （436KB）（296）       Knowledge map    Save COVID-19 pandemic has put a huge burden on public health and global economy. Vaccines play an important role in controlling virus transmission and reducing mortality. While monoclonal virus neutralizing antibodies can reduce the viral load, improve symptoms, and prevent the aggravation of the disease from hospitalization. Now hundreds of clinical trials of COVID-19 vaccine and monoclonal neutralizing antibody are in progress. The vaccine focuses on disease prevention, while the neutralizing antibody focuses on disease treatment. There are quite many differences between the two kinds of clinical trials by following different technical guidelines, research purpose, trial design, implementation and outcome assessment. Therefore, it is necessary to summarize the similarities and differences between the clinical trials for the reference of new drug research and development as well as clinical researchers. Related Articles | Metrics

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Inhibitory and scavenging ability of ambroxol combined with levofloxacin on the bacterial biofilm of Klebsiella pneumoniae LI Xiaoning, YU Xiao, HUANG Chenlei, CAO Ruonan, LI Jie, ZHU Guoping Chinese Journal of Clinical Pharmacology and Therapeutics    2021, 26 (10): 1103-1110.   DOI: 10.12092/j.issn.1009-2501.2021.10.002 Abstract （412）      PDF （2791KB）（236）       Knowledge map    Save AIM: To study the inhibitory and scavenging effects of ambroxol combined with levofloxacin on the bacterial biofilm of Klebsiella pneumoniae, and to provide a new strategy to treat and antagonize the formation of the biofilm. METHODS: We collected Klebsiella pneumoniae of different resistance and divided them into sensitive group (wild bacteria group), ESBLs group and CRKP group with 15 strains in each group and performed biological semi-quantitative detection of its biofilm by crystalline violet staining method. After selecting 3 strains with similar membrane yields from each group, we determined the minimum inhibitory concentration (MIC) of ambroxol and levofloxacin against Klebsiella pneumoniae by micro broth dilution method.In addition, we determined the effects of ambroxol in different concentrations on the MIC of levfloxacin by the micrdilution checkerboard techniques and calculated the partial inhibitory concentration index (FIC) to determine the joint effect and select the best synergistic concentration. Finally, the effects of ambroxol and levofloxacin in different concentrations on the inhibition formation test and removal test of Klebsiella pneumoniae biofilm were observed by crystal violet method combined with confocal laser scanning microscopy. RESULTS: We found that all three groups of bacterial biofilms became mature on the 5th day, and the sensitive group was easier to form and produce biofilm more than the ESBLs and CRKP groups (F=3.725, P=0.032). It was showed that the geometric average of levofloxacin MIC value in the three groups decreased significantly. And the selected strains all showed a synergistic effect on the two-drug combination.In the biofilm test, as the concentration of ambroxol increased, its inhibition rate reached more than 75%, but its biofilm removal rate did not reach 70%. CONCLUSION: Our study support that ambroxol combined with levofloxacin can inhibit the bacterial biofilm of Klebsiella pneumoniae early, and its optimal synergistic concentration is 0.49 mg/mL (ambroxol) + 4 μg/mL (levofloxacin). Related Articles | Metrics

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LI Xiaomin, YI Zhiheng, ZHANG Yanxin, XU Sumei, HU Xiaolei, XU Pingsheng, PAN Lin Chinese Journal of Clinical Pharmacology and Therapeutics    2021, 26 (11): 1279-1284.   DOI: 10.12092/j.issn.1009-2501.2021.11.009 Abstract （411）      PDF （870KB）（182）       Knowledge map    Save Related Articles | Metrics

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Literature analysis of the design and results of the First-In-Human clinical trials of drugs from 2009 to 2020 DENG Kunhong, LIU Yaxin, SUN Yuanyuan, CHEN Wenjing, YANG Nan, HU Zhanqing, CHEN Kaifeng, HUANG Jie, XIANG Yuxia, YANG Guoping Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (1): 77-85.   DOI: 10.12092/j.issn.1009-2501.2022.01.011 Abstract （407）      PDF （868KB）（268）       Knowledge map    Save AIM: Describe the general situation of the First-In-Human trials of the drugs, and summarize the design and results of the First-In-Human trials.  METHODS: We searched the literature of the First-In-Human trials in 2009-2020 on PubMed and screened out the literature that met the research purpose. The basic information of the literature was collected. Data analysis was conducted to summarize relevant outcomes. RESULTS: A total of 559 First-In-Human trials were included in this study. The types of drugs included small molecule drugs (52.42%, 293/559), macromolecule drugs (45.62%, 255/559), and a small amount of cells and viruses (1.97%, 11/559) and so on. Regarding the determination of the starting dose, whether it was in macromolecules (23.86%, 21/88) or small molecules (30.15%, 41/136), No Observed Adverse Effect Level (27.68%, 62/224) was mainly used as the main reference basis, followed by preclinical research (21.88%, 49/224) and Minimal Anticipated Biological Effect Level (8.48%, 19/224), etc. In the dose escalation test, 50.19%(135/269) of the studies used the traditional standard 3+3 dose escalation method, followed by the accelerated titration method (7.06%, 19/269), and the improved 3+3 method (6.69%, 18/269), etc. CONCLUSION: The design of First-In-Human clinical trials has certain regularity in the content and results of the research design. In the subsequent trials, it is important to scientifically design the First-In-Human trials, and promote the safe and effective development of the First-In-Human trials of the drugs. Related Articles | Metrics