Membrane transport of andrographolide in artificial membrane and rat small intestine.
In the present study, the possible drug interactions of andrographolide with co-administering drugs such as acetaminophen, amoxycillin, aspirin, chlorpheniramine and norfloxacin to treat various infectious and inflammatory diseases that may be induced during absorption process were examined using artificial lipophilic membrane and everted rat intestine. The membrane transport of andrographolide across the artificial membrane was not affected by different pH of the medium (simulated gastric and intestinal fluids), different concentrations of andrographolide and co-administered drugs examined. In everted rat intestine, above co-administered drugs examined showed no significant effect on andrographolide membrane transport. The participation of efflux transporters such as P-glycoprotein and MRP2 in andrographolide transport was then examined, since andrographolide is a diterpene compound and some diterpene compounds are known as P-glycoprotein substrates. Cyclosporine, a P-glycoprotein/MRP2 inhibitor, significantly suppressed the efflux transport of andrographolide in distal region of intestine, whereas probenecid, an MRP inhibitor, showed no significant effect in both proximal and distal regions of intestine. These results suggest that P-glycoprotein, but not MRP, is participated in the intestinal absorption of andrographolide and P-glycoprotein-mediated drug interactions occur depending on the co-administered drugs and its concentrations.
Daodee
Supawadee
S
Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand.
Wangboonskul
Jinda
J
Jarukamjorn
Kanokwan
K
Sripanidkulchai
Bung-orn
BO
Murakami
Teruo
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active; D004224:Diterpenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004347:Drug Interactions; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D008567:Membranes, Artificial; D051381:Rats; D017207:Rats, Sprague-Dawley
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; C423013:Abcc2 protein, rat; D004224:Diterpenes; D008567:Membranes, Artificial; C030419:andrographolide