Oral characteristics of bergenin and the effect of absorption enhancers in situ, in vitro and in vivo.
The purpose of this study was to explore the absorption characteristics of bergenin (CAS 477-90-7) and to improve its bioavailability by modulation of the gastrointestinal (GI) absorption using two enhancers (borneol and Poloxamer 188, resp. F68) based on in situ absorption model, in vitro Caco-2 monolayer and in vivo pharmacokinetics studies and comparing the results obtained. The effect of borneol and F68 on drug absorption was quantified at two concentration levels (1 or 4 mg/ml). The observations from in situ and in vitro model indicated that the oral absorption of bergenin is limited and passive diffusion could be the main manner. After oral administration alone (60 mg/kg), a biphasic characteristic was observed. AUC0-->infinity was only 1.95 +/- 0.29 microg x h/ml and Cmax was 0.44 +/- 0.11 microg/ml. From the results of in situ experiments, both of the enhancers were able to increase the absorption percentage of bergenin. Significantly increased (P < 0.05) apparent permeability was observed in Caco-2 cell monolayer. The oral bioavailability of bergenin in rats was improved in the presence of borneol or F68. AUC0-->infinity increased significantly (P < 0.05) to 8.61 +/- 3.74 and 3.41 +/- 1.17 microg x h/ml, which were 4.42 and 1.75-fold higher with borneol and F68 than that of the control group, respectively. The enhanced bioavailability suggests that borneol and F68 could promote the absorption of bergenin in the GI tract.
Qin
Xuan
X
Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, The People's Republic of China.
Yuan
Fang
F
Zhou
Dan
D
Huang
Yuan
Y
D000818:Animals; D000897:Anti-Ulcer Agents / Q000493:pharmacokinetics*; D001578:Benzopyrans / Q000493:pharmacokinetics*; D001682:Biological Availability; D018938:Caco-2 Cells; D001892:Camphanes / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008297:Male; D020442:Poloxamer / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013056:Spectrophotometry, Ultraviolet
D000897:Anti-Ulcer Agents; D001578:Benzopyrans; D001892:Camphanes; D020442:Poloxamer; C006741:bergenin; C022871:isoborneol