1.Prescription investigation for potential adverse drug interactions based on pharmacokinetics of gefitinib and establishment of review rules
Jun CHENG ; Long WANG ; Fuguo SI ; Guanjun ZHANG
China Pharmacy 2025;36(12):1511-1514
OBJECTIVE To analyze the potential adverse drug interactions based on pharmacokinetics (PK-pADIs) of gefitinib, and establish its corresponding prescription review rules. METHODS Outpatient prescriptions of gefitinib combination therapy in our hospital from January 1, 2022 to November 30, 2024 were collected through rational drug software system. PK- pADIs present in the prescriptions were identified based on the Drugs.com® drug interactions database. The specific combination drugs and cases of PK-pADIs were statistically analyzed, and prescription review rules were established according to the severity classification of PK-pADIs. RESULTS & CONCLUSIONS A total of 217 prescriptions of gefitinib combination therapy were enrolled. Among them, 28 prescriptions (12.90%), involving a total of 28 patients, had 29 cases of PK-pADIs, with respiratory medicine prescriptions (22 prescriptions) being the main type. The combination drugs included proton pump inhibitors (13 cases), strong cytochrome P450 3A4 (CYP3A4) inhibitors (7 cases), H2 receptor antagonists (4 cases), CYP3A4 inducers (3 cases), and CYP2D6 substrates (2 cases). The severity classifications for these interactions were severe, moderate, severe, moderate and moderate, respectively. Based on the above severity classification of PK-pADIs, four prescription review rules had been established as follows: when gefitinib was combined with acid-suppressing drugs, it should be subject to “manual review”; when gefitinib was combined with dexamethasone, metoprolol, or strong CYP3A4 inhibitors, an “alert” should be triggered, and the physician should be informed via an alert box to strengthen the monitoring of relevant indicators. Clinical pharmacists need to conduct in-depth training on knowledge related to gefitinib drug interactions in key clinical departments such as respiratory medicine. They should strengthen the monitoring and guidance of rational drug use for patients who are on long-term gefitinib therapy, and promptly identify and intervene in PK-pADIs, thereby enhancing the rationality, safety, and effectiveness of clinical drug use.
2.Expressions of miR-27a-3p mRNA and YAP1 mRNA in Breast Cancer and the Relationship With Clinicopathology and Survival Prognosis
Zhizhong LU ; Xiling LI ; Kai LI ; Siwei YANG ; Fuguo JIANG ; Shuai LI ; Haiyan SI ; Junmin LI ; Xiaoguang ZHAO
Journal of Sichuan University (Medical Sciences) 2025;56(2):521-527
Objective To analyze the expression levels of miR-27a-3p mRNA and Yes-associated protein 1(YAP1)mRNA in breast cancer,and to explore their relationships with clinicopathological features and the survival prognosis of patients.Methods A total of 130 breast cancer patients who underwent mastectomy in our hospital between January 2019 and January 2021 were enrolled.The expression levels of miR-27a-3p and YAP1 mRNA in breast tumor tissues and adjacent normal breast tissues were assessed by qRT-PCR.Furthermore,the relationships between their expression and clinicopathological features,as well as the survival prognosis of patients,were investigated.Results Compared with adjacent normal breast tissues,the expression of miR-27a-3p mRNA in breast tumor tissues was lower(P<0.05),while that of YAP1 mRNA was higher(P<0.05).A negative correlation was observed between the expression of miR-27a-3p mRNA and YAP1 mRNA in breast tumor tissues(r=-0.456,P<0.05).The expression of miR-27a-3p mRNA was correlated with tumor diameter,histological grade,tumor staging by the TNM system,lymph node metastasis,and vascular invasion in patients with breast cancer(P<0.05).The YAP1 mRNA expression was correlated with histological grade,tumor staging by the TNM system,lymph node metastasis,and vascular invasion(P<0.05).Kaplan-Meier survival analysis revealed that the 3-year overall survival rate of the miR-27a-3p low-expression group was 71.60%(48/67),which was lower than the 91.50%(54/59)of the miR-27a-3p high-expression group(log-rank x2=8.211,P=0.004).The 3-year overall survival rate of the YAP1 high-expression group was 73.80%(45/61),lower than that of the YAP1 low-expression group(87.70%,57/65)(log-rank x2=4.429,P=0.035).Multivariate regression analysis indicated that lymph node metastasis(hazard ratio[HR]=1.409;95%CI,1.057-1.644;P=0.046),vascular invasion(HR=1.541;95%CI,1.076-1.869;P=0.045),low miR-27a-3p mRNA expression(HR=0.593;95%CI,0.388-0.925;P=0.018),and high YAP1 mRNA expression(HR=0.628;95%CI,0.405-0.912;P=0.022)were relevant factors affecting the 3-year overall survival of patients with breast cancer.Conclusion A significant downregulation of miR-27a-3p mRNA and upregulation of YAP1 mRNA are observed in breast tumor tissues.The low expression of miR-27a-3p mRNA and the high expression of YAP1 mRNA are associated with adverse clinicopathological features and poor survival prognosis,and are risk factors affecting the 3-year overall survival of patients with breast cancer.They show promise as new potential therapeutic targets for breast cancer.

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