Study of effect of rifampin and tanshinone II A on pravastatin transport via BSEP in sandwich-cultured rat hepatocytes / 中国药理学通报

ABSTRACT

Aim To elucidate the effect of rifampin and tanshinone II A on BSEP transport capacity using pravastatin as the BSEP substrate in sandwich-cultured rat hepatocytes (SCRH). Methods SCRH model was established. The doses of drugs were determined by MIT. A HPLC-MS/MS method was developed and was conducted method validation to detect the concentration of pravastatin. The effect of rifampin and tanshinone D A on the concentration of pravastatin in the bile duct was investigated. And the biliary excretion index ( BEI) was calculated. Results The SCRH model was successfully developed. The appropriate doses of rifampin, tanshinone DA, glibenclamide and pravastatin were determined. A stable and reliable HPLC-MS/MS method for the determination of pravastatin was established Compared with blank control group, rifampin reduced the concentration of pravastatin in the bile duct and the BEI of pravastatin. The high concentration of rifampin caused the steepest downward trends ( P < 0 . 0 1 ) . Compared with high concentration group of rifampin, the concentration of pravastatin in the bile duct and the BEI of pravastatin gradually increased after the combination of rifampin and tanshinone II A, and the effect of high concentration of tanshinone II A was the most significant ( P < 0. 0 1 ) . Conclusions Rifampin could inhibit the function of BSEP in SCRH. The combination of tanshinone D A and rifampin could reverse the inhibitor)' effect of BSEP transport capacity caused by rifampin.