title: [Intestinal absorption of forsythoside A by rat circulation in situ].
abstract: This study is to investigate the effects of concentration, intestinal section, pH, paracellular route, substrate/inhibitor of enzyme (CYP3A) and proteins (P-gp, MRP2, SGL1) on the absorption of forsythoside A. The absorption of three concentrations (2.6, 5.2, and 10.4 microg x mL(-1)) of forsythoside A in different intestinal segments was studied with phenol red as the marker by rat circulation in situ. The results showed that the residue of forsythoside A with different concentrations had little significant difference from that obtained after perfusing via duodenum, jejunum, ileum and colon, which indicated that the absorption of forsythoside A was passive diffusion and had no difference in different segments of rat intestine. The residue of forsythoside A increased to 466.160 and 463.429 microg respectively when cyclosporine (4 microg x mL(-1)) or midazolam (50 micromol x L(-1)) was added to the circulation fluid, which showed significant difference compared to the control group (P < 0.05). Moreover, the residue of forsythoside A showed a tendency of increase with the increase of cyclosporine or midazolam. When digoxin (50 micromol x L(-1)) or EDTA (10 microg x mL(-1)) was added to the circulation fluid, the residue of forsythoside A decreased to 325.110 and 369.888 microg respectively, which showed significant difference as compared to the control group (P < 0.05). Besides, the residue of forsythoside A showed a tendency of reduction with the increase of digoxin or EDTA. However, there is no significant change in the absorption of forsythoside A when the different concentrations of mannitol were added to the circulation fluid. The results above indicated that the absorption of forsythoside A was mainly passive diffusion and involved paracellular route at the same time. In addition, the substrates of P-gp or CYP3A had dose-dependent effect on the absorption of forsythoside A.
authors.affiliation: College ofPharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Liu-Qing
authors.initials: LQ
authors.lastname: Di
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Bi
authors.forename: Le-Tian
authors.initials: LT
authors.lastname: Chen
authors.forename: Qiu
authors.initials: Q
authors.lastname: Du
mesh_terms: D000818:Animals; D003106:Colon / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D004077:Digoxin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000378:metabolism; D004492:Edetic Acid / Q000494:pharmacology; D006027:Glycosides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D007082:Ileum / Q000378:metabolism; D007408:Intestinal Absorption; D007583:Jejunum / Q000378:metabolism; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D008874:Midazolam / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006027:Glycosides; D008353:Mannitol; D004077:Digoxin; D016572:Cyclosporine; D004492:Edetic Acid; C058049:forsythiaside; D008874:Midazolam