Studies On The Pharmacokinetics Of Puerarin And Self-Microemulsifying Drug Delivery Systems Soft Capsule Of Pueraria Lobata

Puerarin is one of the main active constituents of Pueraria lobata, and it has been used for the treatment of senile ischemic cerebrovascular disease.The main objectives of this research were to study the intestinal absorption and first-pass effect of puerarin, pharmacokinetic changes of coadministration with other drugs in rats, to prepare the Self-microemulsifying drug delivery systems (SMEDDS) of Pueraria lobata and to research its pharmacokinetics in different animals.The intestinal transport of puerarin was performed by applying everted intestinal sacs method. With an increase of the concentration of puerarin, puerarin absorption across intestinal membrane was increased in the rat jejunum, ileum and colon, but there exited a saturable transport process for puerarin. pH values didn't affect intestinal absorption of puerarin in different sacs. Tween-80 and Transcutol P increased the intestinal absorption of puerarin, and 1,2-Propanediol had no effect on the intestinal absorption of puerarin. With an increase of the concentration of verapamil and digoxin, puerarin absorption across intestinal membrane increased in the rat jejunum, ileum and colon, but when the concentration of digoxin and verapamil was 50 and 200 μg/ml, the increase had a saturable process, so it was indicated that the transport of puerarin across intestinal membrane was mediated by efflux transport.The Caco-2 cell model was used to study the transport of puerarin across the intestinal membrane. The transport of puerarin across Caco-2 cell monolayers was directional. With the increase of the concentration of puerarin, the permeability coefficient ratio (PDR) was decreased from 2.1 to 1.4. With the increase of temperature, PDR was increased. When KCN and 2,4-dinitrophenol were added, the permeability coefficient ratio was decreased from 1.7 to 1.0 and 1.2, respectively. When 100 μg/ml verapamil was added, the permeability coefficient of apical to basolateral was increased from 0.84±0.18×10^-7 cm/s to 1.01 ±0.17×10^-7 cm/s, and the permeability coefficient of basolateral to apical was decreased from 1.43±0.18×10^-7 cm/s to 1.11 ±0.24×10^-7 cm/s. From the everted intestinal sacs and Caco-2 cell models, it was proved that puerarin was transported across intestinal membrane by efflux pump-P-glyprotein.The hepatic clearance of puerarin during isolated rat liver perfusion were 0.511 ±...