Role of the Efflux Transporters BCRP and MRP1 in Human Placental Bio-disposition of Pravastatin.

Role of the Efflux Transporters BCRP and MRP1 in Human Placental Bio-disposition of Pravastatin. Biochem Pharmacol. 2018 Sep 11;: Authors: Afrouzian M, Al-Lahham R, Patrikeeva S, Xu M, Fokina V, Fischer WG, Abdel-Rahman SZ, Costantine M, Ahmed MS, Nanovskaya T Abstract The expression and activity of human placental transporters during pregnancy could be altered by several factors including pathological changes associated with preeclampsia. The aims of this study were to identify the placental efflux transporters involved in the bio-disposition of pravastatin, determine the protein expression of these transporters and their encoding genes as well as the activity of pravastatin uptake in placentas obtained from patients with preeclampsia. ATP-dependent uptake of [3H]-pravastatin by trophoblast tissue apical and basal membrane vesicles exhibited sigmoidal kinetics. The curved shapes of Eadie-Hofstee plots indicate that more than one placental transporter are involved in the uptake of pravastatin. ATP-dependent uptake of [3H]-pravastatin into vesicles expressing MRP1-5, BCRP, and P-gp, as well as the results of inhibition studies suggest that BCRP and MRP1 are the major placental efflux transporters responsible for the in vitro uptake of pravastatin. Compared to placentas from healthy pregnancies, preeclamptic placentas had increased number of syncytial knots with increased expression of BCRP in their apical membrane and increased expres...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research