Assessment of intestinal absorption of vitexin-2''-o-rhamnoside in hawthorn leaves flavonoids in rat using in situ and in vitro absorption models.
The purpose of this study was to investigate the absorption mechanism of vitexin-2''-O-rhamnoside, the index component in hawthorn leaves flavonoids (HLF) in the rat intestine, using two different absorption models, the in situ single-pass intestinal perfusion and the in vitro everted gut sac model. The effective permeability coefficients (P(eff)) in the in situ single-pass intestinal perfusion experiments and the apparent permeability coefficients (P(app)) in the in vitro everted gut sac experiments were calculated. Furthermore, the influences of the P-glycoprotein inhibitors, verapamil and digoxin, on the intestinal absorption of vitexin-2''-O- rhamnoside in HLF were studied using the above-mentioned two models. Results showed that there were no significant differences in the absorption of vitexin-2''-O-rhamnoside in HLF in four segments of the rat intestine, duodenum, jejunum, ileum, and colon, and at different concentrations of HLF ranging from 0.05 mg/ml to 0.5 mg/ml (P > 0.05). The P(eff) values for vitexin-2''-O-rhamnoside in the rat jejunal perfusion at the concentration of 0.05, 0.1, 0.25, and 0.5 mg/ml were (2.48 +/- 0.33) x 10(-5); (2.23 +/- 0.67) x 10(-5); (2.18 +/- 0.48) x 10(-5); and (2.25 +/- 0.17) x 10(-5) cm/s, respectively. But there was significant difference between absence and presence of verapamil or digoxin (P < 0.05). P(eff) and P(app) values of vitexin-2''-O-rhamnoside in HLF were increased in the presence of verapamil or digoxin. In conclusion, vitexin-2''-O-rhamnoside can be classified into high permeability class drug according to the biopharmaceutical classification system. Passive diffusion dominates the absorptive transport behavior of vitexin-2''-O-rhamnoside in HLF. The absorption and secretion are mediated by the efflux transport system, P-gp. The absorption of vitexin-2''-O-rhamnoside in HLF can be enhanced administered together with P-gp inhibitors.
Xu
Ying-ai
YA
Shanghai Key Laboratory for Pharmaceutical Metabolite Research, School of Pharmacy, Second Military Medical University, Shanghai, PR China.
Fan
Guorong
G
Gao
Shen
S
Hong
Zhanying
Z
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors; D000818:Animals; D047310:Apigenin / Q000493:pharmacokinetics*; D027825:Crataegus; D004077:Digoxin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005419:Flavonoids / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D008297:Male; D018515:Plant Leaves; D051381:Rats; D017207:Rats, Sprague-Dawley; D014700:Verapamil / Q000494:pharmacology
D018435:ATP Binding Cassette Transporter, Subfamily B; D005419:Flavonoids; C021329:vitexin rhamnoside; D004077:Digoxin; D047310:Apigenin; D014700:Verapamil