The Biological Fate of Pharmaceutical Excipient β-Cyclodextrin: Pharmacokinetics, Tissue Distribution, Excretion, and Metabolism of β-Cyclodextrin in Rats

• Published in: Molecules (Basel, Switzerland) Switzerland), 2022-02, Vol.27 (3), p.1138
• Main Authors: Mu, Kunqian, Jiang, Kaiwen, Wang, Yue, Zhao, Zihan, Cang, Song, Bi, Kaishun, Li, Qing, Liu, Ran
• Format: Article
• Language: English
• Subjects: Animals; beta-Cyclodextrins - metabolism; beta-Cyclodextrins - pharmacokinetics; Blood flow; Carbon dioxide; Chromatography, High Pressure Liquid; Colon; Cyclodextrins; Dextromethorphan; Drugs; Excipients; Excipients - metabolism; Excipients - pharmacokinetics; Excretion; Flow velocity; In vivo methods and tests; Ingredients; LC-MS/MS; Male; Maltodextrin; Mass spectrometry; Metabolism; Metabolites; Oral administration; Organs; Pharmaceuticals; Pharmacokinetics; Pharmacology; Plasma; Quality control; Quality standards; Quantitative analysis; Rats; Rats, Wistar; Safety engineering; Scientific imaging; Software; Spleen; Tandem Mass Spectrometry; Tissue Distribution; Ultrastructure; Urine; β-Cyclodextrin
• ISSN: 1420-3049; 1420-3049
• 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 H O. 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.