title: Role of glucose transporters in the intestinal absorption of gastrodin, a highly water-soluble drug with good oral bioavailability.
abstract: Gastrodin, a sedative drug, is a highly water-soluble phenolic glucoside with poor liposolubility but exhibits good oral bioavailability. The current study aims to investigate whether glucose transporters (GLTs) are involved in the intestinal absorption of gastrodin. The intestinal absorption kinetics of gastrodin was determined using the rat everted gut sac model, the Caco-2 cell culture model and the perfused rat intestinal model. In vivo pharmacokinetic studies using diabetic rats with high GLT expression were performed. Saturable intestinal absorption of gastrodin was observed in rat everted gut sacs. The apparent permeability (Papp) of gastrodin from the apical (A) to basolateral (B) side in Caco-2 cells was two-fold higher than that from B to A. Glucose or phlorizin, a sodium-dependent GLT (SGLT) inhibitor, reduced the absorption rates of gastrodin from perfused rat intestines. In vivo pharmacokinetic studies showed that the time of maximum plasma gastrodin concentration (Tmax) was prolonged from 28 to 72 min when orally co-administered with four times higher dose of glucose. However, the Tmax of gastrodin in diabetic rats was significantly lowered to 20 min because of the high intestinal SGLT1 level. In conclusion, our findings indicate that SGLT1 can facilitate the intestinal absorption of gastrodin.
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Cai
authors.forename: Juan
authors.initials: J
authors.lastname: Huang
authors.forename: Hui
authors.initials: H
authors.lastname: Luo
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Lei
authors.forename: Zhaoxiang
authors.initials: Z
authors.lastname: Yang
authors.forename: Yang
authors.initials: Y
authors.lastname: Mai
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D001592:Benzyl Alcohols / Q000493:pharmacokinetics* / Q000494:pharmacology; D001682:Biological Availability; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism*; D005960:Glucosides / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism*; D012995:Solubility
chemical_list: D001592:Benzyl Alcohols; D051246:Glucose Transport Proteins, Facilitative; D005960:Glucosides; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; C045345:gastrodin; D005947:Glucose