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  • Shi-yu LI, Huai-chen SHENG, Chong-fa ZHAO
    Chinese Journal of Clinical Pharmacology. 2025, 41(16): 2251-2256.
    Objective

    To observe the clinical efficacy and safety of preoperative medication with lidocaine hydrochloride injection ultrasonic atomization combined with low-dose dexmedetomidine hydrochloride injection for fiberoptic bronchoscopy under general anesthesia in patients with pulmonary tuberculosis.

    Methods

    Patients with pulmonary tuberculosis scheduled for general anesthesia fiberoptic bronchoscopy were randomly divided into treatment group and control group. Both groups were given intravenous infusions of fentanyl citrate injection 0.05 mg and 1.5 mg·kg-1 propofol medium and long chain fat emulsion injection for induction of anesthesia. During the procedure, 2-3 mg·kg-1·h-1 propofol medium and long chain fat emulsion injection was used to maintain anesthesia. Control group received no additional treatment, while treatment group received an additional intravenous infusion of 0.2 μg·kg-1 dexmedetomidine hydrochloride injection through micro-pump over 15 min, combined with nebulized inhalation of lidocaine hydrochloride injection 3-4 mL, before induction of anesthesia. The postoperative anesthesia status, recovery quality, inflammation-related indicators and safety were compared between the two groups.

    Results

    Among the 95 patients with pulmonary tuberculosis who underwent fiberoptic bronchoscopy under general anesthesia, 3 cases dropped out during the treatment and finally 46 cases were included in each group. After treatment, the loss of consciousness time in control group and treatment group were (172.65±36.81) and (146.67±26.46)s, respectively; the recovery time were (18.67±1.06) and (15.50±0.75) min, respectively; the orientation recovery time were (16.63±1.76) and (9.57±1.70) min and the dosage of propofol were (130.21±13.41) and (124.02±15.43) mg, respectively; the Ramsay scores of 10 minutes after awakening were (3.09±0.51) and (2.57±0.62) points, respectively; the Ramsay scores of 20 minutes after awakening were (3.52±0.55) and (3.00±0.67) points, respectively; the levels of death-associated protein kinase 1 (DAPK1) were (88.08±9.85) and (81.88±11.55) ng·L-1, respectively; the levels of NOD-like receptor family pyrin domain-containing 3 (NLRP3) were (78.63±9.35) and (73.96±7.52) ng·L-1, respectively; the levels of interleukin-1β (IL-1β) were (46.02±4.59) and (41.04±6.62) ng·L-1, respectively and the levels of IL-18 were (5.71±1.64) and (4.78±1.23) ng·L-1, respectively. The differences of the above indexes between treatment group and control group were statistically significant (all P<0.05). The main adverse drug reactions of control group were tinnitus, dizziness, nausea, agitation and convulsion; in treatment group were dizziness, nausea, agitation and convulsion, the total incidence of adverse drug reactions in control group was 13.04% (6 cases/46 cases), while that in treatment group was 8.70% (4 cases/46 cases). There was no statistically significant difference between the two groups (P>0.05).

    Conclusion

    Lidocaine hydrochloride injection combined with low-dose dexmedetomidine hydrochloride injection has significant advantages in patients with pulmonary tuberculosis undergoing fiberoptic bronchoscopy under general anesthesia. It can effectively improve the anesthetic effect and recovery quality of patients, reduce the dosage of propofol and reduce the levels of inflammatory factors with with good safety.

  • Jiao-jiao ZUO, Rui-ze WANG, Wen-ting WANG, Rui-ping SONG, Peng-cheng DOU, Xin-yi CHEN, Zhuang-zhuang FENG, Jin SHU
    Chinese Journal of Clinical Pharmacology. 2025, 41(16): 2393-2400.

    Precancerous lesions of gastric cancer (PLGC) are considered as a high-risk factor for the development of gastric cancer. Existing studies have confirmed that hypoxia inducible factor-1α (HIF-1α) plays a key role in the progression of PLGC. HIF-1α promotes the malignant transformation of PLGC by regulating various cellular processes, including angiogenesis, aerobic glycolysis, autophagy, cell proliferation, and apoptosis. Traditional Chinese medicine (TCM) has been shown to modulate the HIF-1α signaling pathway and inhibit these pathological processes, thereby intervening in the development of PLGC. This review will focus on the mechanisms by which HIF-1α mediates PLGC and summarize the potential applications of TCM in the prevention and treatment of PLGC, aiming to provide a clear molecular framework for TCM intervention in PLGC and offer theoretical support and research directions for the development of innovative HIF-1α-targeted Chinese medicines.

  • Shun ZENG, Yi-tao LIN, Hao ZHOU, Ying PAN, Miao YU
    Chinese Journal of Clinical Pharmacology. 2025, 41(16): 2269-2274.
    Objective

    To analyze the effect of urapidil sustained release capsules combined with finasteride tablet in the treatment of benign prostatic hyperplasia with lower urinary tract symptoms.

    Methods

    Patients with benign prostatic hyperplasia accompanied by lower urinary tract symptoms were included and randomly divided into treatment group and control group. Both groups received basic treatment with finasteride tablets, 5 mg each time, once daily, orally. The treatment group was treated with urapidil sustained release capsules, with an initial dose of 30 mg per day. If the patient’s clinical symptoms did not improve within 1-2 weeks, the dose could be gradually increased to 60 mg per day, with a maximum dose not exceeding 60 mg per day, twice a day, orally. Control group did not receive additional treatment. Compare the improvement of symptoms, quality of life, urodynamic indicators, laboratory indicators, clinical efficacy and evaluate safety between two groups.

    Results

    A total of 45 patients in treatment group and control group were included respectively. Ten patients withdrew from the study due to lost to follow-up or personal factors during the study, 5 patients in each groups. Finally, a total of 80 patients completed the study, 40 patients in treatment group and 40 patients in control group. The total effective rate of treatment group was 95.00% (38 cases/40 cases), while that of control group was 80.00% (32 cases/40 cases), which was statistically significantly higher in treatment group than in control group (P<0.05). After treatment, the international prostate symptom score (IPSS) of treatment group and control group were (10.52±0.98) and (13.79±1.05) points; the prostate quality of life score (QoL) were (2.01±0.77) and (2.51±0.52) points, above indicators in treatment group were statistically significantly lower than those in control group (all P<0.05). After treatment, post-void residual urine volume (PVR) levels of treatment group and control group were (31.60±3.75) and (35.79±3.24) mL, respectively; the average urinary flow rates (AER) were (16.88±1.46) and (14.37±1.22) mL·s-1, respectively; the maximum urinary flow rates (Qmax) were (24.09±2.03) and (21.96±2.77) mL·s-1, respectively. The PVR level in treatment group was statistically significantly lower than that in control group, while the AER and Qmax levels were statistically significantly higher than those in the control group (all P<0.05). After treatment, the prostate-specific antigen (PSA) levels in treatment group and control group were (0.51±0.09) and (0.74±0.10) ng·L-1, respectively; the numbers of red blood cells in urine sediment were (37.41±3.06) and (40.25±3.22) cells per HP, respectively, and the above indicators in treatment group were statistically significantly lower than those in control group (all P<0.05). After treatment,the testosterone (T) levels in treatment group and control group were (974.05±16.87) and (929.78±16.77) ng·mL-1, respectively; the estradiol (E2) levels were (136.47±10.55) and (127.58±10.35) pg·mL-1, respectively. The above indicators in treatment group were significantly higher than those in control group (all P<0.05). The main adverse drug reactions in both groups were gastrointestinal discomfort, headache, etc. The incidence of adverse drug reactions in treatment group was 12.50% (5 cases/40 cases), while in control group was 5.00% (2 cases/40 cases). There was no statistically significant difference between the two groups (P>0.05).

    Conclusion

    Patients with benign prostatic hyperplasia accompanied by lower urinary tract symptoms were treated with combination therapy of urapidil sustained-release capsules and finasteride tablet, which improved their urodynamic indicators and clinical symptoms, restored their sex hormone levels, improved their treatment efficacy and quality of life.

  • Guan-hua LIANG, Guang-bin ZHONG, Chang LIU, Mei-xing YAN, Xiao-mei MO
    Chinese Journal of Clinical Pharmacology. 2025, 41(16): 2346-2350.

    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.

  • Yin-yin WANG, Ting-ting CHEN, Xue-ting WANG, Ling TAO, Xiang-chun SHEN, Min ZHANG
    Chinese Journal of Clinical Pharmacology. 2025, 41(16): 2311-2316.
    Objective

    To investigate the effects of gastrodin (GAS) on diabetes-induced cardiomyopathy (DCM) and its underlying mechanisms.

    Methods

    Fifty C57BL/6J mice were divided into control group (n=10, normal diet) and high-fat high-sucrose (HFD) group [n=40, HFD diet combined with intraperitoneal streptozotocin (STZ) injection to establish the DCM model]. Successfully modeled HFD mice were randomly assigned to the model group, GAS low-dose group (50 mg·kg-1, qd), GAS high-dose group (100 mg·kg-1 qd), and positive control metformin group (250 mg·kg-1qd). The control and model groups were administered saline via gavage, while the other three groups received their respective drugs via gavage for three consecutive months. Cardiac ultrasound was used to measure left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-systolic volume (LVESV), and left ventricular internal diameter at end-systole (LVIDs). Serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were quantified using assay kits. Cardiac tissue levels of malondialdehyde (MDA) and glutathione (GSH) were measured. Protein expression was analyzed via Western blotting.

    Results

    The LVEF of the model group and high-dose group were (62.54±3.24)% and (80.20±3.29)%, respectively, and the LVFS were (25.87±4.75)% and (42.97±4.75)%, respectively LVESVs were (55.00±4.08) and (23.75±4.79) μL, LVIDs were (2.63±0.16) and (1.67±0.21) mm, TG was (1.17±0.18) and (0.51±0.09) mmol·L-1, TC was (5.58±0.76) and (1.93±0.58) mmol·L-1, HDL-C was (1.69±0.50) and (4.86±0.48) mmol·L-1, LDL-C was (3.84±0.70) and (1.17±0.65) mmol·L-1, respectively. The MDA content was (6.10±0.38) and (3.02±0.16) nmol· mgprot-1, the GSH content was (20.90±10.30) and (39.49±15.70) μmol·gprot-1, the relative expression levels of oxidative stress protein Kelch like ECH associated protein 1 (Keap1) were 1.75±0.22 and 1.07±0.03, the relative expression levels of nuclear factor-E2-related factor 2 (Nrf2) were 0.51±0.09 and 0.96±0.13, and the relative expression levels of peroxidase-1 (PRDX-1) were 0.43±0.08 and 0.93±0.18, respectively, and the relative expression levels of heme oxygenase-1 (HO-1) were 0.42±0.08 and 0.94±0.14, respectively. Compared with the model group, the above indicators in the high-dose group showed statistically significant differences (P<0.01,P<001).

    Conclusion

    GAS can improve the myocardial function of DCM mice, and its mechanism of action may be related to the inhibition of oxidative stress and the regulation of the Keap1/Nrf2 signaling pathway.

  • Jing-han ZHANG, Tao ZUO, Lei ZHAO
    Chinese Journal of Clinical Pharmacology. 2025, 41(16): 2386-2392.

    The treatment of posterior segment diseases has always been a challenge in the field of ophthalmology. How to overcome obstacles in drug delivery and improve the bioavailability of drugs in the posterior segment of the eye is one of the most challenging aspects in the field of drug research. The innovation of drug delivery routes and dosage forms, as well as breakthroughs in drug development, have brought new hope for the delivery of drugs in the posterior segment of the eye. This article reviews three aspects of innovative drug delivery routes for subretinal drug delivery, suprachoroidal drug delivery, and vitreous cavity implantation, innovative drug delivery form design for nano-formulations and exosomal formulations, and innovative drug development for intraocular injections, topical drops, and oral drugs, with the aim of providing new strategies for the treatment of diseases of the posterior segment of the eye.

  • Ming HUANG, Xiao-ming SUN, Xiao-yu SUN, Jing-qi ZHOU
    Chinese Journal of Clinical Pharmacology. 2025, 41(16): 2340-2345.
    Objective

    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.

    Methods

    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.

    Results

    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.

    Conclusion

    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.

  • Chun-qing WANG, Zhi-jie CHEN, Ying-li ZHANG
    Chinese Journal of Clinical Pharmacology. 2025, 41(16): 2257-2262.
    Objective

    To study the efficacy and safety of allisartan isoproxil tablet combined with indapamide tablet in the treatment of patients with mild to moderate essential hypertension and coronary heart disease.

    Methods

    Patients with mild to moderate essential hypertension and coronary heart disease were divided into treatment group and control group using the cohort method. The control group was given oral indapamide tablets 2.5 mg once a day based on the conventional treatment regimen. The treatment group was given allisartan isoproxil tablets 240 mg once a day in addition to the control group’s regimen for a total of 12 weeks. The clinical efficacy, 24-hour blood pressure variability, cardiac function, vascular endothelial function and safety evaluation of the two groups were compared.

    Results

    A total of 105 patients were enrolled, including 54 patients in treatment group and 51 patients in control group. After treatment, the total clinical effective rate of the treatment group was 90.74% (49 cases/54 cases), and that of control group was 72.55% (37 cases/51 cases), which was significantly higher in treatment group than in control group (P<0.05). After treatment, the daytime (d) systolic blood pressure variability (SBPV) levels in treatment group and control group were (11.32±2.13) and (12.48±2.26) mmHg, respectively; the nighttime (n) SBPV levels were (10.03±1.79) and (10.82±2.10) mmHg, respectively; the d diastolic blood pressure variability (DBPV) levels were (8.66±1.51) and (9.36±1.57) mmHg, respectively; the nDBPV levels were (8.05±1.32) and (8.68±1.62) mmHg, respectively; the 24 h SBPV levels were (10.85±2.20) and (11.96±2.05) mmHg, respectively; the 24 h DBPV levels were (9.67±1.93) and (10.66±1.92) mmHg, respectively; the brain natriuretic peptide (BNP) levels were (83.47±10.53) and (89.41±13.19) ng·L-1, respectively; the endothelin-1 (ET-1) levels were (55.44±9.27) and (60.36±10.86) ng·L-1, respectively; and the Apelin levels were (36.44±6.41) and (34.22±4.37) ng·mL-1, respectively. The above metrics showed significant differences between the two groups (P<0.05,P<0.01). The adverse drug reactions in treatment group included diarrhea, fever, fatigue, palpitations, soreness in both knee joints, cough, insomnia, decreased appetite and orthostatic hypotension. The adverse drug reactions in control group included diarrhea, headache, decreased appetite, insomnia and orthostatic hypotension. The total incidence of adverse drug reactions in treatment group was 22.22% (12 cases /54 cases), and that in control group was 17.65% (9 cases /51 cases). There was no statistically significant difference (P>0.05).

    Conclusion

    The application of allisartan isoproxil combined with indapamide in treatment of patients with mild to moderate essential hypertension and coronary heart disease can achieve significant therapeutic effects, regulate 24-hour blood pressure variability, improve cardiac function, vascular endothelial function, and quality of life, also demonstrate good safety.

  • Zhen-zhen ZHU, Ying XIE, Feng-xia DU, Li-wei LANG, Qian-yu LI, Jing ZHANG, Fang WANG
    Chinese Journal of Clinical Pharmacology. 2025, 41(16): 2281-2286.
    Objective

    To investigate the influence of augmented renal clearance (ARC) on the steady-state serum concentration and pharmacodynamics of meropenem in patients with severe infections and to analyze the linear relationship between them.

    Methods

    A retrospective analysis was conducted on the inpatients who received meropenem treatment and underwent therapeutic drug monitoring (TDM) at the Fifth Medical Center of the General Hospital of the PLA from June 2021 to September 2024. Serum drug concentration data were collected, and pharmacokinetic parameters were calculated using a one-compartment model. The steady-state serum concentrations and pharmacodynamic parameters were compared between patients with normal renal function and those with ARC. Multiple linear regression analysis was performed to explore the factors influencing meropenem serum concentrations and pharmacodynamic parameters.

    Results

    When meropenem was administered at a dose of 1.0 g three times daily, the blood concentrations in patients with ARC at 3 hours and 0.5 hours before the last administration were (4.78±2.34) mg·L-1 and (2.44±1.60) mg·L-1, respectively. In contrast, the corresponding concentrations in patients with normal renal function were (14.08±10.45) mg·L-1 and (8.40±7.07) mg·L-1, respectively. The blood concentrations of meropenem were significantly lower in ARC patients compared to those with normal renal function (P<0.05). For the pharmacodynamic target of f%T>4MIC≥40%, the target attainment rates in ARC patients were 81.25%, 25.00%, 0.00%, and 0.00% at MIC values of 1, 2, 4, and 8 μg·mL-1, respectively. In comparison, the rates in patients with normal renal function were 92.31%, 76.92%, 53.85%, and 7.69%, respectively, indicating significantly lower target attainment in the ARC group. Multiple linear regression analysis revealed that creatinine clearance rate and serum albumin level significantly influenced both the plasma concentration and pharmacodynamic target attainment of meropenem.

    Conclusion

    ARC significantly reduces the steady-state serum concentration of meropenem and the rate of achieving pharmacodynamic targets, leading to the failure of anti-infective therapy. For patients with severe infections and ARC, attention should be paid to the effects of creatinine clearance, serum albumin on serum drug concentrations and therapeutic efficacy. TDM should be performed to adjust the dosing regimen in a timely manner.

  • Ting-zhao LIU, Wang HU, Wen ZHANG, Feng ZHANG, Sheng-long ZHANG, Yang CAO, Shun-wang HUANG, Huan ZHOU
    Chinese Journal of Clinical Pharmacology. 2025, 41(16): 2330-2334.
    Objective

    To 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.

    Methods

    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.

    Results

    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%.

    Conclusion

    In the state of fasting and fed single oral administration, the two kinds of vortioxetine hydrobromide tablets have good bioequivalence.