[Advances in the study of excipient inhibitors of intestinal P-glycoprotein].
P-glycoprotein (P-gp) located in the apicalmembranes of intestinal absorptive cells is an energy-dependent efflux pump which can reduce the bioavailability of a wide range of substrate drugs. There is increasingly interest in enhancing the bioavailability of these molecules by inhibiting intestinal P-gp. A classification of excipient inhibitors of intestinal P-gp nonionic surfactants, poly (ethylene glycol), derivates of beta-cyclodextrin and thiolated chitosan will be presented and then the inhibition mechanism will be discussed. Compared with traditional P-gp inhibitor, excipient inhibitors appear to have minimal nonspecific pharmacological activity, thus potential side effects can be mostly avoided. These excipient inhibitors, which hold the promise of replacing the traditional ones, will be extensively employed to significantly improve the intestinal absorption of poorly soluble and absorbed drugs as a result of P-gp inhibition, and thus to enhance the bioavailability of these drugs. However, the further studies of both the mechanism and clinical application are urgently needed.
Yan
Fang
F
School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Si
Lu-Qin
LQ
Huang
Jian-Geng
JG
Li
Gao
G
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics; D000818:Animals; D001682:Biological Availability; D002686:Chitin / Q000031:analogs & derivatives / Q000494:pharmacology; D005079:Excipients / Q000494:pharmacology*; D005990:Glycerol / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D011092:Polyethylene Glycols / Q000494:pharmacology; D013501:Surface-Active Agents / Q000494:pharmacology*; D047392:beta-Cyclodextrins / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005079:Excipients; D013501:Surface-Active Agents; D047392:beta-Cyclodextrins; C493042:chitosan-4-thiobutylamidine; D002686:Chitin; D011092:Polyethylene Glycols; C000515:cremophor EL; C031215:betadex; D005990:Glycerol