Intestinal absorption of forsythoside A by rat circulation in situ.
- Author:
Wei ZHOU
1
;
Liu-Qing DI
;
Xiao-Lin BI
;
Le-Tian CHEN
;
Qiu DU
Author Information
1. College ofPharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Colon;
metabolism;
Cyclosporine;
pharmacology;
Digoxin;
pharmacology;
Dose-Response Relationship, Drug;
Duodenum;
metabolism;
Edetic Acid;
pharmacology;
Glycosides;
administration & dosage;
pharmacokinetics;
Hydrogen-Ion Concentration;
Ileum;
metabolism;
Intestinal Absorption;
Jejunum;
metabolism;
Male;
Mannitol;
pharmacology;
Midazolam;
pharmacology;
Rats;
Rats, Sprague-Dawley
- From:
Acta Pharmaceutica Sinica
2010;45(11):1373-1378
- CountryChina
- Language:Chinese
-
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.
