Latest ArticlesTo evaluate the bioequivalence of the test preparation and the reference preparation in a single dose of vortioxetine hydrobromide tablets under fasting and fed conditions in healthy volunteers.
A randomized, open-ended, single-dose, two-cycle, double-cross bioequivalence trial design was adopted, and 28 subjects were enrolled in the fasting group and the fed group, respectively, and 1 tablet of the test preparation and the reference preparation were taken in the fasting or fed state each cycle. The concentration of vortioxetine in plasma was determined by liquid chromatography-tandem mass spectrometry （LC-MS/MS） method. The main pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.1, and the bioequivalence was evaluated.
The t1/2 for the fasting single oral administration of the test preparation and the reference preparation were （61.74±23.90） and （58.22±18.61）h, the median Tmax were （7.33±2.15） and （7.61±3.89） h, the Cmax were （7.32±1.90） and （7.46±1.98） ng·mL-1, and the AUC0-72 h were （312.61±92.95） and （310.00±93.84） h·ng·mL-1, respectively. The statistical results of the 90% confidence intervals of the main pharmacokinetic parameters Cmax and AUC0-72 h were 92.75%-103.71% and 97.47%-104.43%, respectively, all of which were within the range of 80.00%-125.00%, and the safety of the tested preparation and the reference preparation was good when taken orally on an empty stomach. The t1/2 of single oral administration after prandial administration of the tested preparation and the reference preparation were （77.60±33.87） and （81.61±45.24） h, the median Tmax were （8.06±3.02） and （7.77±2.45）h, the Cmax were （7.54±2.08） and （7.76±2.00） ng·mL-1, and the AUC0-72 h were （319.75±87.71） and （326.03±86.64） h·ng ·mL-1, respectively. The 90% confidence intervals of Cmax, AUC0-72 h were 89.00%-105.32% and 92.21%-102.72%, respectively, which were in the range of 80.00%-125.00%.
In the state of fasting and fed single oral administration, the two kinds of vortioxetine hydrobromide tablets have good bioequivalence.
To evaluate the bioequivalence and safety of colchicine tablets under fasting and fed conditions in Chinese healthy participants.
A single-center, randomized, open, single-dose, two-formulation, two-period, two-sequence crossover design was adopted, enrolling 72 healthy participants, with 36 healthy participants in each group for fasting and fed conditions. Single oral dose 0.5 mg of test formulation (T) or the reference formulation (R) was taken across two periods，respectively. Plasma concentration of colchicine was determined using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The pharmacokinetic parameters were calculated and the bioequivalence was evaluated using the non-compartmental model in Phoenix WinNonlin 8.2 software.
The main pharmacokinetic parameters of a single oral colchicine tablet under fasting condition for T and R were as follows: Cmax were (2.70±0.88) and (2.54±0.87) ng·mL-1，tmax were 0.98 (0.48, 2.00) and 0.98 (0.73, 2.48) h，t1/2 were (29.54±5.46) and (29.67±4.86) h，AUC0-t were (18.40±5.30) and (18.00±5.10) h·ng·mL-1，AUC0-∞ were (21.80±5.90) and (20.70±4.90) h·ng·mL-1, respectively. The main pharmacokinetic parameters under fed condition for T and R were as follows: Cmax were (2.49±0.84) and (2.58±1.00) ng·mL-1，tmax were 1.48 (0.73, 3.98) and 1.48 (0.73, 4.00) h，t1/2 were (31.79±4.69) and (30.65±4.91) h，AUC0-t were (19.80±4.30) and (19.90±5.00) h·ng·mL-1，AUC0-∞ were (23.20±5.00) and (23.10±5.20) h·ng·mL-1, respectively. The geometric mean ratios of Cmax, AUC0-t and AUC0-∞ of the T and R formulations under fasting and fed conditions with a 90% confidence interval ranged from 80.00% to 125.00%.
Under both fasting and fed conditions, the colchicine tablet test formulation and reference formulation were bioequivalent in Chinese healthy subjects, and both were shown to be safe.
To establish and validate a highly sensitive and selective high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the determination of lurasidone, which was used subsequently to clinical lurasidone blood drug concentration monitoring.
Tadalafil was used as internal standard. Following a deproteinization procedure, lurasidone and the internal standard (tadalafil) were isostatically eluted using a mobile phase composed of methanol and 0.1% aqueous formic acid (50：50, v/v) at a flow rate of 0.70 mL·min-1. The chromatographic separation was achieved within 4.0 min on an Agilent ZORBAX Eclipse plus C8(4.6 mm×100.0 mm，3.5 μm). Quantification was performed using a triple-quadrupole mass spectrometer operating in positive electrospray ionization (ESI) mode with multiple reaction monitoring (MRM). The method was validated for selectivity, linearity (calibration curve), precision and accuracy, matrix effect, extraction recovesise, stability and dilutive integrity. The concentrations of 14 clinical samples were measured after this method was validated.
The calibration curve for lurasidone in human plasma demonstrated linearity over the concentration range of 0.50-500.00 ng·mL-1. The precision data (both intra- and inter-day) for the three QC levels ranged from 2.87% to 10.03%. Accuracy (relative error) was within±15% of the nominal values. The plasma samples maintained stability for 28 h at room temperature, for 85 days at -20 ℃ and through five freeze-thaw cycles. The measured concentrations of clinical samples were within the range of the standard curve, with concentrations ranging from 2.63 to 21.17 ng·mL-1.
The validated method is proved to be convenient, accurate, and sensitive for the quantification of lurasidone in human plasma. The method is proved to be suitable for the monitoring of plasma concentration and pharmacokinetics study of lurasidone.
A 76 years old female patient was hospitalized twice for pulmonary infection and bronchiectasis with infection. During her first admission to the respiratory department for pulmonary infection, she received intravenous cefoperazone sodium/sulbactam sodium combined with bronchodilators for 11 days and was discharged following clinical improvement, with no documented adverse drug reactions (ADRs). During her second presentation to the emergency department for bronchiectasis exacerbation, the patient developed cyanosis and profuse sweating 13 minutes after intravenous cefoperazone/sulbactam administration. Despite successful resuscitation and subsequent transfer to the intensive care unit (ICU), emergency physicians failed to recognize this event as a suspected drug hypersensitivity reaction or document it in the medical records. After 11 days of meropenem therapy and symptomatic management in the ICU, she was transferred back to the respiratory department. Respiratory physicians initiated antibiotic de-escalation by readministering cefoperazone/sulbactam, which precipitated respiratory distress, profuse sweating and systemic discomfort within 19 minutes, followed by loss of consciousness and cardiopulmonary arrest. The patient died after 48 hours of unsuccessful resuscitation. This case serves as a reminder that the sensitization period for drugs can persist from several days to several months. The absence of ADRs with previous use does not entirely preclude the risk of subsequent administration. The recognition of hypersensitivity is critical, necessitating enhanced vigilance among healthcare professionals regarding ADRs. The documentation of ADRs and handover procedures during transfers between departments should not be overlooked to ensure medication safety.
The newly revised The International Council for Harmonizsation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E6 R(3) sets out internationally accepted principles and standards for conducting clinical trials. The application of innovative technologies in clinical trials, consideration of risk proportionality, and the development of new models are all important drivers for the revision of ICH E6 R(3). The main features of this revision include: alignment with “ICH E8 R(1) General Considerations for Clinical Studies,” restructuring of the document, provision of guidance on data governance, encouragement of risk-proportionate and fit-for-purpose approaches, and the establishment of practical and feasible expectations for sponsors and investigators. The revision also adapts to innovations in clinical trial design, technology, conduct, and data sources; strengthens the protection of minor trial participants; emphasizes transparency in clinical trial registration and results reporting; and updates terminology. The revision of ICH E6 R(3) impacts sponsors, investigators, ethics committees, and service providers, offering guidelines that are both practical and flexible, and continuously responding to the rapid development of the clinical trial ecosystem.
Bone-related infections represent a significant challenge in orthopedic practice, and the penetration efficacy of antimicrobials into bone tissue serves as a critical determinant of therapeutic outcomes. This review systematically summarizes the bone penetration characteristics of clinically used antimicrobial agents. Current evidence indicates that most β-lactam antibiotics demonstrate bone penetration rates ranging from 10% to 50%, while fluoroquinolones exhibit higher penetration at 30%-100%. Vancomycin and teicoplanin display penetration rates between 10% and 40%. Notably, clindamycin, linezolid and rifampicin achieve penetration rates exceeding 30%. Multiple factors influence drug penetration characteristics, including anatomical bone site variations, local blood perfusion status, patients’ pathophysiological conditions, as well as administration routes and dosage regimens.
Diabetic kidney disease (DKD) is a clinical syndrome in which diabetes leads to microvascular lesions and then glomerulosclerosis. In the progression of DKD, the hypoxia inducible factor-1α (HIF-1α) signaling pathway is involved in the occurrence, development and pathological formation of DKD. Related studies have shown that the HIF-1α pathway is the most critical pathway for the treatment of DKD with traditional Chinese medicine. Among them, Chinese medicine monomers, Chinese medicine compounds, and Chinese patent medicines play a role in preventing interstitial fibrosis and glomerulosclerosis by regulating the HIF-1α pathway. Its mechanism is closely related to inflammation, oxidative stress, cell apoptosis, and ferroptosis. This article reviews the existing research results on the treatment of DKD with the intervention of traditional Chinese medicine in the HIF-1α pathway in recent years, in order to provide a theoretical basis for the prevention and treatment of DKD and the development of new drugs.
The clinical isolation rate of carbapenem-resistant Acinetobacter baumannii (CRAB) has been increasing year by year, yet effective antimicrobial agents against this pathogen remain severely limited. Sulbactam-durlobactam, a novel β-lactam combination agent, has demonstrated promising in vitro antibacterial activity against CRAB. In May 2023, the U.S. Food and Drug Administration approved its use for patients aged 18 and older to treat hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible isolates of the Acinetobacter baumannii-calcoaceticus complex, providing a new therapeutic option. This article reviews the mechanism of action, pharmacokinetics, pharmacodynamics, and clinical studies of sulbactam-durlobactam based on literature, aiming to offer insights for clinical practice.
Acute lung injury (ALI) is a severe respiratory disease. Given the limited existing treatment methods, it is urgent to explore new therapies. Pyroptosis plays a crucial role in the onset of ALI. Traditional Chinese medicine can regulate the pathways related to pyroptosis, reduce the inflammatory response, and improve acute lung injury, thus providing new strategies for the treatment of ALI. This article systematically reviews the mechanisms by which pyroptosis causes ALI in alveolar macrophages, neutrophils, and pulmonary vascular endothelial cells, summarizes the published literature from 2019 to 2024, and explores the action mechanisms of active ingredients and compound prescriptions of traditional Chinese medicine in the treatment of ALI, aiming to provide a theoretical basis for the research and development of new drugs.
Vancomycin is the first-line drug for treating infections caused by methicillin-resistant gram positive bacteria in patients with malignant hematological diseases. However, due to significant differences in the physiological and pathological characteristics of these patients compared to the general population, the pharmacokinetic behavior of vancomycin in the body may undergo significant changes. These changes may lead to unpredictable therapeutic effects, increased safety risks, and the evolution of bacterial resistance. Personalized dosing strategies may offer potential solutions to address these issues. Nevertheless, at present, there is a lack of unified, guideline-based, or consensus-driven reference standards for personalized dosing in these patients, particularly adult patients, and relevant research data remain insufficient. This review systematically summarizes the current status of pharmacokinetic studies on vancomycin in adult patients with malignant hematological diseases and focuses on the analysis of population pharmacokinetic models and their application progress. Additionally, this paper provides a detailed discussion of the current technical approaches available for vancomycin personalized dosing, including techniques based on therapeutic drug monitoring, clinical decision support systems, novel technical methods, and the latest dynamic dosing techniques developed by our research team based on individualized dosing models. Through an organized review of existing research, this paper identifies the challenges faced in achieving broader implementation of personalized dosing. It is hoped that this study will provide valuable insights for achieving personalized vancomycin dosing in patients with malignant hematological diseases, thereby advancing clinical practice and technological development in this field.
No. 86 Xueyuan South Road, Haidian District, Beijing
010-62662699(Operation and Technical Support)
qkjq@cast.org.cn
Copyright © 2025 China Association for Science and Technology. All rights reserved. For all open access content, the relevant licensing terms apply.
Sponsored by the Office of the Leading Group for Cybersecurity and Informatization of CAST, and supported by Science and Technology Review Publishing House
