Drug-Drug interactions of docetaxel in patients with breast cancer based on insurance claims data.

Despite an increase in the use of targeted anticancer drugs and immunotherapy, cytotoxic anticancer drugs such as docetaxel continue to play a clinically important role. The aim of this study was to evaluate drug-drug interactions between docetaxel and coadministered medicines in patients with breast cancer a claims database. The Health Insurance Review and Assessment Service (HIRA) database (2017 to 2019) was used in this study. We evaluated the risk of neutropenia (defined using receipt of granulocyte colony-stimulating factor (G-CSF) prescriptions) under docetaxel administration or the coadministration of docetaxel and an interacting anticancer drug (predefined based on approval information obtained from the Korean Ministry of Food and Drug Safety and the Lexicomp electronic database). The propensity score matching method was applied to balance covariates in the case (patients with G-CSF prescriptions) and control (patients without G-CSF prescriptions) groups. We identified 947 female patients with breast cancer prescribed with docetaxel and excluded 321 patients based on inclusion criteria. Of the remaining 626 patients, 280 were assigned to the case group and 346 to the control group. Predefined drugs were coadministered to 71 (11.3%) patients during the 7-day period before and after the administration of docetaxel. Adjusted odds ratios (ORs) calculated using the logistic regression model applied to the propensity score matching showed no significant difference between the administration of docetaxel alone and docetaxel coadministration (adjusted OR, 2.010; 95% confidence interval, 0.906, 4.459). In conclusion, we suggest that coadministration of docetaxel and a predefined interacting drug are not associated with G-CSF prescription.

Anti-inflammatory activity of ethanol extract derived from Phaseolus angularis beans.

ETHNOPHARMACOLOGICAL SIGNIFICANCE: Phaseolus angularis Wight (adzuki bean) is an ethnopharmacologically well-known folk medicine that is prescribed for infection, edema, and inflammation of the joints, appendix, kidney and bladder in Korea, China and Japan. AIM OF STUDY: The anti-inflammatory effect of this plant and its associated molecular mechanisms will be investigated. MATERIALS AND METHODS: The immunomodulatory activity of Phaseolus angularis ethanol extract (Pa-EE) in toll like receptor (TLR)-activated macrophages induced by ligands such as lipopolysaccharide (LPS), Poly (I:C), and pam3CSK was investigated by assessing nitric oxide (NO) and prostaglandin (PG)E(2) levels. To identify which transcription factors such as nuclear factor (NF)-κB and their signaling enzymes can be targeted to Pa-EE, biochemical approaches including reporter gene assays, immunoprecipitation, kinase assays, and immunoblot analyses were also employed. Finally, whether Pa-EE was orally available, ethanol (EtOH)/hydrochloric acid (HCl)-induced gastritis model in mice was used. RESULTS: Pa-EE dose-dependently suppressed the release of PGE(2) and NO in LPS-, Poly(I:C)-, and pam3CSK-activated macrophages. Pa-EE strongly down-regulated LPS-induced mRNA expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2. Interestingly, Pa-EE markedly inhibited NF-κB, activator protein (AP)-1, and cAMP response element binding protein (CREB) activation; further, according to direct kinase assays and immunoblot analyses, Pa-EE blocked the activation of the upstream signaling molecules spleen tyrosine kinase (Syk), p38, and transforming growth factor ß-activated kinase 1 (TAK1). Finally, orally administered Pa-EE clearly ameliorated EtOH/HCl-induced gastritis in mice. CONCLUSION: Our results suggest that Pa-EE can be further developed as a promising anti-inflammatory remedy because it targets multiple inflammatory signaling enzymes and transcription factors.