School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
School of Food and Drug, Shenzhen Polytechnic, 7098 Lau sin Avenue, Shenzhen 518115, China.
Molecules. 2022 Feb 8;27(3):1138. doi: 10.3390/molecules27031138.
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 CO and HO. 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.
β-环糊精具有独特的环形中空超微结构，能够将各种水溶性较差的药物包裹在其形成的腔内，从而提高药物的稳定性。作为一种生物活性分子，β-环糊精的代谢主要由结肠中的菌群完成，其可以与 API 相互作用。在这项研究中，为了便于同时定量分析药物辅料β-环糊精和 API 右美沙芬氢溴酸盐，我们开发了一种 LC-MS/MS 方法来了解β-环糊精的体内命运。该方法已成功用于研究大鼠口服β-环糊精后的药代动力学、组织分布、排泄和代谢。结果表明，β-环糊精在 36 小时内几乎从大鼠血浆中完全清除，并且在给药后，β-环糊精迅速分布到血流速度增加的器官，如脾、肝和肾，浓度较高。完整的β-环糊精经尿液和粪便排泄的量低于给药剂量。可以推测，β-环糊精代谢为麦芽糊精，然后进一步代谢、吸收，并最终以 CO 和 HO 的形式排出。结果表明，β-环糊精在体内相对低积累，具有良好的安全性。这些结果将有助于进一步研究辅助β-环糊精的设计和安全性评价，并促进其临床开发。
