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

Authors :
Mu K
Jiang K
Wang Y
Zhao Z
Cang S
Bi K
Li Q
Liu R
Source :
Molecules (Basel, Switzerland) [Molecules] 2022 Feb 08; Vol. 27 (3). Date of Electronic Publication: 2022 Feb 08.
Publication Year :
2022

Abstract

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 <subscript>2</subscript> and H <subscript>2</subscript> 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.

Details

Language :
English
ISSN :
1420-3049
Volume :
27
Issue :
3
Database :
MEDLINE
Journal :
Molecules (Basel, Switzerland)
Publication Type :
Academic Journal
Accession number :
35164401
Full Text :
https://doi.org/10.3390/molecules27031138