Dose-adjusted concentrations of Posaconazole oral suspension in hematopoietic stem cell transplantation patients and analysis of the influential factors / 中国药房

OBJECTIVE To analyze the dose-adjusted concentrations of Posaconazole oral suspension in patients undergoing hematopoietic stem cell transplantation （HSCT） and their influential factors. METHODS Data were collected from hospitalized HSCT patients admitted to the First Affiliated Hospital of Shandong First Medical University （Shandong Provincial Qianfoshan Hospital） from January 2021 to April whtwhm@yeah.net 2023 who took Posaconazole oral suspension for the prevention of invasive fungal disease （IFD） and received blood concentration of posaconazole. The rate of concentration attainment and clinical failure rate of posaconazole for the prevention of IFD were evaluated， and one-way and multiple linear regression analyses were performed for the influential factors of dose-adjusted concentrations （C0/D） of posaconazole. RESULTS A total of 44 patients were enrolled； the mean C0 of posaconazole in patients was （0.99±0.94） µg/mL， and 20 patients had a C0≥0.7 μg/mL， with a concentration attainment rate of 45.45% for the prevention of IFD； 13 cases were clinical failures， with a clinical failure rate of 29.55%. Of 24 patients who did not achieve C0/D of posaconazole for IFD prophylaxis， one patient was a clinical failure despite timely dose adjustment of posaconazole in seven patients； seven of the thirteen patients who did not undergo dose adjustment were clinical failures； and the remaining four patients were switched to other antifungal agents. The results of univariate analysis showed that gender， body mass index （BMI）， renal function， combined use of sodium phenytoin， omeprazole and metoclopramide had a significant effect on the C0/D of posaconazole （P＜0.05）； the results of multivariate linear regression analysis showed that gender， BMI and combined use of sodium phenytoin were the independent factors affecting the C0/D of posaconazole （P＜0.05）. CONCLUSIONS Significant individual differences are reflected in the blood concentration of Posaconazole oral suspension； gender， BMI and combined use of sodium phenytoin are independent factors affecting the C0/D of posaconazole.

Efficacy and safety of aerosol inhalation of polycolistin B in patients with severe pneumonia combined with mechanical ventilation / 中国药房

OBJECTIVE To investigate the efficacy and safety of aerosol inhalation of polycolistin B in the treatment of severe pneumonia combined with mechanical ventilation， and to provide a reference of real-world data for clinical drug therapy. METHODS A retrospective cohort study was conducted to analyze the clinical data of 87 patients with severe pneumonia combined with mechanical ventilation at the First Affiliated Hospital of Shandong First Medical University from January 2021 to February 2023. According to route of administration， all patients were divided into combined group （24 cases， receiving aerosol YXH2021ZX013） inhibition of polycolistin B combined with intravenous dripping） and routine group （63 cases， intravenous dripping of polycolistin B alone）. The differences in efficacy （mortality，clinical response rate and bacterial clearance rate）and safety （elevated serum creatinine， bronchospasm and skin pigmentation） were compared between two groups； the influential factors of primary outcome index as mortality were analyzed through univariate analysis and multivariate Logistic regression analysis. RESULTS In terms of efficacy， there were no statistical differences in mortality（37.50% vs. 41.27%， P＝0.749）， clinical response rate （54.17% vs. 55.56%， P＝0.907） and bacterial clearance rate （45.83% vs. 44.44%， P＝0.907） between the two groups. In terms of safety， the incidence of bronchospasm in the combined group was significantly higher than that of the routine group （12.50% vs. 0， P＝0.028）， but the differences in incidence of elevated serum creatinine and skin pigmentation between two groups were not statistically significant （P＞0.05）. Univariate analysis showed that the moralities were higher in the case of infected with Acinetobacter baumannii， Klebsiella pneumoniae and combined use of quinolones （P＜0.05）； multivariate Logistic regression analysis showed that infection with A. baumannii （OR＝3.36， P＝0.014） and combined use of quinolones （OR＝3.54， P＝0.013） were independently associated with mortality （P＜0.05）. CONCLUSIONS For severe pneumonia patients with mechanical ventilation， intravenous dripping of polycolistin B combined with aerosol inhalation does not show superior efficacy compared with intravenous dipping of polycolistin B alone， but significantly increases the incidence of bronchospasm. Infection with A. baumannii and combined use of quinolones are independent risk factors for the increase of mortality.

Research progress of selective mGluR1 antagonists / 药学学报

As an important member of metabotropic glutamate receptors (mGluR), metabotropic glutamate receptor 1 (mGluR1) plays an important role in the signal transduction of central nervous system. Selective mGluR1 antagonists can block the signaling pathway activated by mGluR1 and exert a series of physiological actions including analgesia, antianxiety, antidepression, etc. Currently, the discovery and modification of selective mGluR1 antagonists have become a hot research focus. This paper reviews the structural catalogs of selective mGluR1 antagonists and their structure-activity relationships in the last decade.