β-cyclodextrin has a unique annular hollow ultrastructure that allows encapsulation of various poorly water-soluble drugs in the resulting cavity, thereby increasing drug stability. As a bioactive molecule, the metabolism of β-cyclodextrin is mainly completed by the flora in the colon, which can interact with API. In this study, understanding the in vivo fate of β-cyclodextrin, a LC-MS/MS method was developed to facilitate simultaneous quantitative analysis of pharmaceutical excipient β-cyclodextrin and API dextromethorphan hydrobromide. The established method had been effectively used to study the pharmacokinetics, tissue distribution, excretion, and metabolism of β-cyclodextrin after oral administration in rats. Results showed that β-cyclodextrin was almost wholly removed from rat plasma within 36 h, and high concentrations of β-cyclodextrin distributed hastily to organs with increased blood flow velocities such as the spleen, liver, and kidney after administration. The excretion of intact β-cyclodextrin to urine and feces was lower than the administration dose. It can be speculated that β-cyclodextrin metabolized to maltodextrin, which was further metabolized, absorbed, and eventually discharged in the form of CO2 and H2O. Results proved that β-cyclodextrin, with relative low accumulation in the body, had good safety. The results will assist further study of the design and safety evaluation of adjuvant β-cyclodextrin and promote its clinical development.

Background and Objective. Xuefu Zhuyu decoction has good efficacy in both stable and unstable angina pectoris; however, the reasons for this remain elusive. We propose a systematic process to investigate the effectiveness of the formula and the underlying material basis and mechanism of action. Methods. Firstly, we used a network proximity approach to calculate and compare the effectiveness of the formula with that of Western drugs for each type of angina, including all targets and intersecting targets, from a topological perspective. Secondly, we compared the mechanisms of action of the two angina pectoris at three levels and five aspects, including conventional and modular analysis approaches. Thirdly, based on the unique functions of each angina in the complex heterogeneous network, we designed a reverse process for finding the material basis using dynamic, static, and enriched items as well as a total item. Finally, the designed inverse process, material basis, and mechanism of action were validated. Results. The target network of Xuefu Zhuyu decoction is closer to the target network of each type of angina than that of Western drugs, and the intersection targets have a closer proximity. Comparison of the mechanisms of action showed that stable angina and unstable angina had 158 common targets, while the unique targets were 34 and 1, respectively. Modularity analysis showed that the GO similarity of target modules was highly correlated with KEGG similarity. We ended up with 67 compounds upregulated for stable angina and 47 compounds upregulated for unstable angina. Our results were validated by literature mining, high-volume molecular docking, and miRNA enrichment analysis. Conclusions. For both types of angina pectoris, Xuefu Zhuyu decoction is superior to Western drugs. A comparison of various aspects led to the unique mechanisms of action, from which the material basis of each type of angina was deduced.

Nephrotoxicity occasionally occurs during treatment with immune checkpoint inhibitors (ICIs). Few related studies compare the differences between these drugs. This study aimed to systematically characterize nephrotoxicity after ICI initiation. Data were extracted from the US FDA Adverse Event Reporting System (FAERS) database. Disproportionality analysis, including information components (ICs) and reporting odds ratios (RORs), was performed to determine the potential renal toxicity of ICIs. A total of 7,204 reports of renal adverse events (AEs) were identified in the FAERS database. Renal AEs were most commonly reported for nivolumab (46.84%). Strong signals were detected in male patients combined with ICIs. In the clinical application of ICIs, attention should be paid to patients, especially male patients, with acute kidney injury, nephritis, autoimmune nephritis and other nephrotoxic AEs. The use of ICIs is likely to aggravate their condition.