To establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determining the plasma concentration of the active component polymyxin E in patients treated with colistimethate sodium.

Polymyxin B1 was used as an internal standard, and solid phase extraction (SPE) was employed to process the samples. The chromatographic column was a Kinetex C₁₈ (3 mm×100 mm, 2.6 μm). Mobile phase A was an aqueous solution containing 0.1% formic acid and 5 mmol·L^-1 ammonium acetate, and mobile phase B was a methanol solution containing 0.1% formic acid. Gradient elution was performed at a flow rate of 0.5 mL·min^-1. An electrospray ionization (ESI) source was used with positive ion multiple reaction monitoring (MRM) for detection. The ion pairs for quantitative analysis were as follows: m/z 585.6→241.1 (polymyxin E1), m/z 578.6→227.2 (polymyxin E2), and m/z 602.6→101.2 (polymyxin B1). The selectivity, standard curve, residues, precision and accuracy, extraction recovery rate, matrix effect and stability of the method were investigated, and the plasma concentrations of polymyxin E1 and E2 in patients treated with colistimethate sodium were measured.

The linear relationships of polymyxin E1 and E2 concentrations were good within the ranges of 0.02–3.86 μg·mL^-1 and 0.03–5.65 μg·mL^-1, respectively. The lower limits of quantification (LLOQ) for polymyxin E1 and E2 were 0.02 μg·mL^-1 and 0.03 μg·mL^-1, respectively. The standard curve equations for polymyxin E1 and E2 are Y=4.55×10^-1X-2.92×10^-2 (r=0.994 2)、Y=8.61×10^-1X-1.38×10^-2 (r=0.996 4), respectively. The within-day and day-to-day precision, accuracy, extraction recovery, matrix effects, and stability of polymyxin E1 and E2 all met the methodological requirements. Using this method, the AUC of polymyxin E in 26 patients receiving colistimethate sodium ranged from 28.42 to 317.51 μg·mL^-1.

This method is accurate, sensitive, rapid, and stable, and can be used for the determination of the plasma concentrations of polymyxin E1 and E2 in human plasma.

To investigate the etiological factors and clinical characteristics of statin-associated myopathy in elderly patients.

A retrospective analysis was performed on elderly patients with statina-ssociated myopathy who were treated in the internal medicine department of our hospital from January 2017 to June 2024. Data including etiology, clinical manifestations, treatment process and prognosis were collected and analyzed.

A total of 21 elderly patients with statina-ssociated myopathy were enrolled, including 13 males and 8 females, with an average age of (77.33±9.61) years. Among them, 5 patients were diagnosed with rhabdomyolysis. According to the type of statin taken, patients were divided into 5 groups: atorvastatin group, rosuvastatin group, simvastatin group, pitavastatin group and Xuezhikang group. All patients received monotherapy without overlapping or combined use of different statins. The duration of statin therapy at onset ranged from 2 weeks to 10 years. Precipitating factors included infection, concomitant medications, stress and exercise. Among them, 12 cases were related to infection (9 pneumonia, 2 urinary tract infections, 1 intestinal infection), and 2 cases were associated with concomitant medications (quetiapine and cyclosporine A, respectively). Most patients had multiple comorbidities: hypertension in 90.48% (19 cases/21 cases), type 2 diabetes mellitus in 66.67% (14 cases/21 cases), coronary heart disease in 47.62% (10 cases/21 cases), and chronic kidney disease in 23.81% (5 cases/21 cases). Patients were on multiple concomitant medications, with a mean of 6 drugs used. Acute kidney injury occurred in 4 patients with myopathy and in 5 patients with rhabdomyolysis. After comprehensive treatment including statin discontinuation, fluid replacement, urine alkalinization and blood purification, all patients improved and no deaths occurred. Serum creatinine in patients with acute kidney injury returned to normal or baseline levels before onset.

Elderly patients with acute infection, concomitant medications and multiple comorbidities should be closely monitored for the risk of statinassociated myopathy or rhabdomyolysis. Acute kidney injury is common in such elderly patients. Early discontinuation of statins and comprehensive treatment including symptomatic fluid infusion and blood purification can significantly improve patient prognosis.

To observe the clinical efficacy and safety of ezetimibe tablets or alirocumab injection in conjunction with rosuvastatin calcium tablets for the treatment of coronary heart disease (CHD).

Patients with CHD were randomly divided into two groups. Both groups took rosuvastatin calcium tablets, 10 mg once daily. The control group additionally received ezetimibe tablets,10 mg once daily, while the treatment group received alirocumab injection (subcutaneous injection, 75 mg per dose, once every two weeks). After 6 months of treatment, the two groups were compared in terms of clinical efficacy, lipid metabolism, cardiac function and myocardial injury markers. Adverse drug reactions during treatment were recorded.

This study enrolled a total of 118 patients, with 59 assigned to treatment group and 59 to the control group. During the 6-month treatment period, 4 patients in the control group dropped out due to changes in their condition. In treatment group, 6 patients dropped out, comprising 3 due to changes in the treatment plan and 3 who voluntarily withdrew from the study midway. Ultimately, 55 patients in the control group and 53 in the treatment group were included in the final analysis. After treatment, the total clinical effective rates were 90.57% (48 cases/53 cases) in treatment group and 72.73% (40 cases /55 cases) in control group, with statistically significant difference (P<0.05). After treatment, the cholesterol levels in the treatment and control groups were (2.58±0.40) and (3.60±0.52) mmol·L^-1, respectively; low-density lipoprotein cholesterol levels were (2.16±0.36) and (2.51±0.44) mmol·L^-1, respectively; N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were (301.12±20.11) and (326.54±25.84) pg·mL^-1, respectively; cardiac troponin Ⅰ (cTnⅠ) levels were (0.53±0.19) and (0.90±0.26) μg·L^-1, respectively; matrix metalloproteinase-9 (MMP-9) levels were (31.04±4.05) and (37.25±4.72) ng·mL^-1, respectively; left ventricular ejection fraction (LVEF) were (49.79±5.33)% and (45.09±5.21)%, respectively; left ventricular end-diastolic diameter (LVEDD) were (50.36±3.23) and (55.11±3.48) mm, respectively; and left ventricular end-systolic diameter (LVESD) were (35.04±3.72) and (40.64±3.97) mm, respectively. The aforementioned indicators in treatment group showed statistically significant differences compared to control group (all P<0.05). Adverse drug reactions in control group included 2 cases of nausea and vomiting, 2 cases of diarrhea, 3 cases of fatigue and 2 cases of arthralgia. Treatment group reported 2 cases of nausea and vomiting, 3 cases of diarrhea, 2 cases of fatigue, 1 case of arthralgia and 2 cases of injection site redness and swelling. The overall incidence rates of adverse drug reactions in treatment and control groups were 18.87% (10 cases/53 cases) and 16.36% (9 cases/55 cases), respectively, with no statistically significant difference (P>0.05).

Both ezetimibe tablets and alirocumab injection demonstrate good therapeutic efficacy in the treatment of coronary heart disease. However, the combination of alirocumab injection with rosuvastatin calcium tablets can further improve lipid metabolism and cardiac function.

To analyze the steady state plasma concentrations and dose-corrected concentration(C/D) influencing factors of vortioxetine tablets in patients with depression, and to provide guidance in the practice of rational clinical use of vortioxetine tablets in patients with depression.

Patients with depression who took vortioxetine and underwent therapeutic drug monitoring of blood concentrations in our hospital from March 2022 to November 2024 were selected as the study subjects, and their blood concentrations were monitored. Laboratory indicators, demographic information and the effect of coadministration on dose-corrected concentrations of vortioxetine tablets were statistically analyzed by SPSS 26.0.

A total of 90 patients were enrolled, and 107 sessions of blood concentration monitoring were performed. In depressed patients, the steady state plasma concentration was (28.05±20.28) ng·mL^-1, the administered daily dose was (14.86 ± 5.21) mg·d^-1, and the dose-corrected concentration was (1.96±1.24) ng·mL^-1·mg^-1·d. 69.16% (74 cases/107 cases) of C/D exceeded the upper limit of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie(AGNP) guideline reference range. The body weight, alanine aminotransferase(ALT), and urea, as well as the combination of paliperidone, aripiprazole, or clozapine all had a significant effect on the dose-corrected concentration of vortioxetine (all P<0.05). Multiple linear regression analysis revealed that body weight and the combination of aripiprazole had a significant effect on vortioxetine C/D (F=8.517, R²=0.148, P<0.001).

When vortioxetine is used clinically, the dosage should be adjusted according to the patient’s body weight. When it is used in conjunction with aripiprazole, regular monitoring of the plasma concentration should be carried out.

To establish a population pharmacokinetic model of amoxicillin and clavulanate potassium tablets in healthy Chinese subjects under fasting condition.

Based on the previously confirmed bioequivalence results, this study retrospectively collected the plasma concentration data of 18 subjects who received the test preparation and 17 subjects who received the reference preparation. The population pharmacokinetic model of amoxicillin was constructed using Phoenix NLME software. The effects of covariates such as gender, age, albumin, serum creatinine, creatine kinase, fasting blood glucose, and total cholesterol on pharmacokinetics were evaluated by forward inclusion and backward elimination methods. Model validation included goodness-of-fit plots, bootstrap method, and visual predictive check (VPC).

The population pharmacokinetic model of amoxicillin in healthy subjects conformed to a two-compartment model with first-order elimination kinetics and lag time, which could well describe the data. Serum creatinine and body mass index (BMI) were significant covariates. The parameters of the final model were as follows: central volume of distribution (V)=51.56 L, peripheral volume of distribution (V₂)=7.65 L; clearance (CL)=39.99 L·h^-1, intercompartmental clearance (CL₂)=1.78 L·h^-1, absorption rate constant (K_a)=1.45 h^-1. Serum creatinine had an impact on CL₂ and K_a, while BMI affected V.

The two-compartment model with first-order elimination kinetics and lag time can better describe the in vivo absorption characteristics of amoxicillin after oral administration of amoxicillin and clavulanate potassium tablets in healthy subjects.

To develop a clinical trial management system (CTMS) to realize full-process review and management of clinical trial projects, research team management, document management, subject management, drug sample management, free medical order management and quality management.

Within the framework of the existing hospital information system, we collaborated with the hospital information center and a commercial software company to design and develop a full-process intelligent information system for clinical trials. Based on WebService, the system was connected to the hospital information system through standardized application programming interfaces (APIs), with the establishment of standard data dictionaries and governance rules to achieve secure data exchange between heterogeneous systems.

The system balanced development costs and functionality, and achieved good application effects. It integrated functions including project process, document management, drug sample management, subject management, free inspection and testing, and quality management, formed a medical database covering the entire project cycle of subjects, and ensured the authenticity and traceability of data.

This system fully leverages the advantages of joint development and informatization, improves the enrollment efficiency and implementation quality of clinical trials, and provides reference experience for other hospitals to implement integrated clinical trial management systems.

To address issues such as low efficiency and poor consistency in the submission of bioequivalence trial data under the Clinical Data Interchange Standards Consortium standards, this study aimed to develop a set of reusable standardized core data sets to improve data preparation efficiency and regulatory submission quality.

A systematic review of multiple approved BE trial projects was conducted, covering different trial designs, dosage forms, and study types. Common data structures and mapping rules were extracted through business analysis, and standardized data set templates covering both SDTM and ADaM layers were developed in strict accordance with CDISC standards.

This study summarized 274 SDTM and 338 ADaM data element-specific attributes applicable to bioequivalence trials. A set of standardized core data sets suitable for most BE trial scenarios was established and successfully applied in a two-formulation, two-period, two-sequence crossover BE study evaluating a gel patch.

The standardized dataset constructed in this study provides a preliminary framework for the standardization of BE trial data, which requires further validation through large-scale applications to clarify its applicability and robustness in enhancing the standardization level and work efficiency of BE trial data processing. It holds significant practical value for ensuring data quality and improving the success rate of submissions, while also serving as a referenceable example for the development of foundational datasets within the industry.