NDLI: Mechanisms Responsible for Poor Oral Bioavailability of Paeoniflorin: Role of Intestinal Disposition and Interactions with Sinomenine

Content Provider	Springer Nature Link
Author	Liu, Zhong Qiu Jiang, Zhi Hong Liu, Liang Hu, Ming
Copyright Year	2006
Abstract	To determine the intestinal disposition mechanisms of paeoniflorin, a bioactive glucoside, and to investigate the mechanisms by which sinomenine increases paeoniflorin bioavailability.A single-pass “four-site” rat intestinal perfusion model and a cultured Caco-2 cell model were employed.In both model systems, paeoniflorin permeability was poor. In the perfusion model, maximal absorption and metabolism of paeoniflorin occurred in duodenum and jejunum, which were significantly decreased by a glucosidase inhibitor gluconolactone (20 mM). On the other hand, paeoniflorin absorption in terminal ileum increased significantly but its metabolism did not in the presence of sinomenine and cyclosporine A. In the Caco-2 cell model, paeoniflorin was transported 48-fold slower than its aglycone (paeoniflorigenin). Absorptive transport of paeoniflorin was significantly (p < 0.05) increased by sinomenine (38%), verapamil (27%), and cyclosporine A (41%), whereas its secretory transport was significantly (p < 0.01) decreased by sinomenine (50%), verapamil (35%) and cyclosporine A (37%). In contrast, MRP inhibitors MK-571 and leukotriene C4 did not affect transport of paeoniflorin. Lastly, sinomenine was also shown to significantly increase the absorptive transport of digoxin (a prototypical p-glycoprotein substrate) and to significantly decrease its secretory transport.Poor permeation, p-gp-mediated efflux, and hydrolysis via a glucosidase contributed to the poor bioavailability of paeoniflorin. Sinomenine (an inhibitor of the p-gp-mediated digoxin efflux) increased paeoniflorin's bioavailability via the inhibition of p-gp-mediated paeoniflorin efflux in the intestine.
Starting Page	2768
Ending Page	2780
Page Count	13
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	23
Issue Number	12
e-ISSN	1573904X
Language	English
Publisher	Springer US
Publisher Date	2006-10-25
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	bioavailability Caco-2 disposition efflux intestinal paeoniflorin p-glycoprotein inhibitor sinomenine Biomedical Engineering Medical Law Biochemistry Pharmacy Pharmacology/Toxicology
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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