Objective To explore the risk factors for voriconazole-induced adverse reactions in patients with acquired immunodeficiency syndrome(AIDS)for screening the high-risk populations and safe use of voriconazole.Methods Retrospective analysis was performed on patients who received voriconazole from January 2020 to December 2023.Demographic details,medical history,laboratory tests,concomitant medications,and adverse reactions of patients were collected from the hospital information system(HIS).The potential risk factors for the adverse reactions induced by voriconazole were analyzed by univariate and logistic multivariate analysis.Receiver operating characteristic(ROC)curve was used to analyze the specificity and sensitivity of the risk factors as predictor.Results A total of 170 patients were included in this study.Adverse drug reaction was reported in 62 patients(36.5％).Central nervous system toxicity,hepatotoxicity,and visual impairment were the most common adverse reactions.Univariate analysis showed that the adverse reactions of voriconazole were significantly associated with C-reactive protein,aspartic aminotransferase,aspartic aminotransferase/alanine aminotransferase,and CD4+T lymphocytes/CD8+T lymphocytes(CD4+/CD8+).Multivariate analysis indicated that CD4+/CD8+was an independent risk factor for voriconazole-induced adverse reactions.ROC curve indicated that CD4+/CD8+had a better predictive capability(AUC=0.756).Conclusions CD4+/CD8+should be monitored closely during voriconazole treatment for fungal infection in patients with AIDS.CD4+/CD8+may be a good predictor for voriconazole-related psychiatric and visual abnormalities and hepatotoxicity.

Objective To explore the risk factors for voriconazole-induced adverse reactions in patients with acquired immunodeficiency syndrome(AIDS)for screening the high-risk populations and safe use of voriconazole.Methods Retrospective analysis was performed on patients who received voriconazole from January 2020 to December 2023.Demographic details,medical history,laboratory tests,concomitant medications,and adverse reactions of patients were collected from the hospital information system(HIS).The potential risk factors for the adverse reactions induced by voriconazole were analyzed by univariate and logistic multivariate analysis.Receiver operating characteristic(ROC)curve was used to analyze the specificity and sensitivity of the risk factors as predictor.Results A total of 170 patients were included in this study.Adverse drug reaction was reported in 62 patients(36.5％).Central nervous system toxicity,hepatotoxicity,and visual impairment were the most common adverse reactions.Univariate analysis showed that the adverse reactions of voriconazole were significantly associated with C-reactive protein,aspartic aminotransferase,aspartic aminotransferase/alanine aminotransferase,and CD4+T lymphocytes/CD8+T lymphocytes(CD4+/CD8+).Multivariate analysis indicated that CD4+/CD8+was an independent risk factor for voriconazole-induced adverse reactions.ROC curve indicated that CD4+/CD8+had a better predictive capability(AUC=0.756).Conclusions CD4+/CD8+should be monitored closely during voriconazole treatment for fungal infection in patients with AIDS.CD4+/CD8+may be a good predictor for voriconazole-related psychiatric and visual abnormalities and hepatotoxicity.

OBJECTIVE To establish a UPLC detection method for simultaneous determination of mycophenolic acid(MPA) and its glucuronide(MPAG) in plasma of rats, and to investigate gender-related pharmacokinetic characteristics of mycophenolic acid. METHODS Twelve SD rats(half male and half female) were intragastrically administrated with 90 mg·kg-1·d-1mycophenolate acetate, and blood was collected from periorbital vein at different time points after administration. Plasma samples were extracted by liquid-liquid extraction and drug concentrations of MPA and metabolite MPAG in plasma were determined using UPLC. The method was developed using Waters BEH C18 column. The gradient elution was performed at a flow rate of 0.35 mL·min-1 with the mobile phase acetonitrile solution (A)-0.1% formic acid aqueous solution(B). The detection wavelength was at 266 nm and column oven temperature was maintained at 40 ℃. The pharmacokinetic parameters were calculated by using DAS 2.0 software. RESULTS The linear relationship between peak area and concentrations of MPA and MPAG were good in the ranges of 0.31-160 µg·mL-1(R2=0.999 8) and 0.62-320 µg·mL-1(R2=0.999 4), respectively. Analytical methods of MPA and MPAG all met the requirements of the methodology. Pharmacokinetic parameters AUC0-t and Cmax of MPA and MPAG in female rats were higher than that in male rats(P<0.05 or P<0.01). In addition, the metabolic rate of genistein[UDP-glucuronosyltransferases(UGT)s substrate] and MPA in male rat liver microsomes were significantly faster than that in female rat liver microsomes. CONCLUSION This developed UPLC method is sensitive, accurate and specific, which is suitable to detect the concentrations of MPA and MPAG in the plasma. The pharmacokinetics of MPA and MPAG in rats are gender different, which may be related to the sex difference of UGTs metabolic enzyme activity.

OBJECTIVE To establish a physiologically-based pharmacokinetic （PBPK） model of amikacin in elderly patients with renal insufficiency. METHODS PK-SIM® software was adopted for model building， optimization and simulation. The physical and chemical properties and pharmacokinetic parameters related to amikacin were collected by literature review. The PBPK model on adults was established and extrapolated to the elderly population based on the built-in human model. Data from clinical PK studies were used to optimize and validate the model. The goodness of fit， relative residual， and mean folding error （MFE） were used to evaluate the performance of forecasting. The final model was employed to simulate the exposure of amikacin in the elderly population with renal insufficiency， and the efficacy and safety of commonly used clinical dosing regimens were evaluated， and the recommended regimens were proposed. RESULTS The established PBPK model of amikacin had good prediction performance in both adult and elderly populations， with the absolute mean of relative residual value of 25%； the MFE of peak concentration （cmax） and area under the plasma concentration curve （AUC0－∞） in all simulation occasions ranged ＞0.5-＜2. The simulation results showed that， compared with healthy adults， no significant clinical difference in cmax was observed in the elderly with renal insufficiency at the same dosing regimen， but the trough concentration increased significantly due to accumulation. Prolonging the administration interval of amikacin rather than reducing the dosage was more helpful to ensure the efficacy and to reduce the occurrence of nephrotoxicity. CONCLUSIONS The PBPK model for amikacin is successfully established in the elderly patient with renal insufficiency， and shows good predictive performance.

Objective To study the therapeutic effects and related mechanism of Tongmai Yizhi granules on vascular dementia in rats. Methods Bilateral carotid artery ligation was used to establish rat model of vascular dementia (VD). The rats were randomly divided into 6 groups: sham operated,the model control,piracetam (0. 375 g·kg-1 ·d-1 ) as positive con-trol,low dose (2. 5 g·kg-1 ·d-1 ),middle dose(5. 0 g·kg-1 ·d-1 ),and high dose (10. 0 g·kg-1 ·d-1 ) of Tongmai Yizhi granules. Each group was intragastrically administered with 10 mL·kg-1 of corresponding medications for 31 days after the VD model was established. The sham group was given with 0. 9% NaCl solution. Y-electric maze was used to test the learning and memory function of rats at the second and fourth weeks. On the day 32,hippocampal tissues were collected for pathological analy-sis by microscope. The activities of SOD and content of MDA in serum and tissue homogenate were tested. Results Compared with model control group,each dose of Tongmai Yizhi granules obviously shortened the incubation period of VD rats in electric maze test,and accuracy of learning and memory was improved (P<0. 05 or P<0. 01). The activity of SOD was decreased,and the content of MDA was increased after treatment with Tongmai Yizhi granules (P < 0. 01). Hippocampal neuronal cells were disar-ranged,and the number of cone cells was decreased significantly in the model control group. In contrast,the necrosis and degener-ation of hippocampal neurons were alleviated in all Tongmai Yizhi treatment groups. Conclusion Tongmai Yizhi granule can apparently improve learning and memory function of VD rats. It can also improve the activity of SOD and reduce the content of MDA in serum and hippocampus,effectively remove free radicals,and alleviate the injury of hippocampal pyramidal cells.

Objective To study the effect of vasopressin (VS) on the small bowel circulation and the safety of emboliotherapy for the small intestinal hemorrhage by DSA. Methods Ten dogs were divided into three groups. Vasa recta were ligated 30min after VS infusion ended in group A( n =4), and 2h after VS infusion ended in group B( n =4), they were ligated without VS infusion in control group ( n =2). DSA were performed before and after VS infusion, before and after the ligation. The tested parts of intestine were resected to make the pathologic examination a week late. Results All branches of mesenteric arteries contracted and the contrast developed light in the intestinal wall after VS infusion. Branches contraction recovered but the contrast developed still slight in the intestinal wall about 30min after infusion ended. All manifestation of DSA recovered to normal 2h after infusion ended. In all groups, the blood vessel net can be seen but is fewer and scattered in the area of ligation. The collorate presented soon after the ligation. The pathologic examination proved that there was only mind mucosal ischemia in all groups. Conclusion The repressive effect of VS to the circulation of intestine weakened and then disappeared rapidly after the infusion ended. VS infusion had no significant effect on the safety of emboliotherapy for small intestinal bleeding when the infusion has been finished for more than 2hr. DSA can demonstrated the circulation state of the intestine before and after embolization.