Functional Consequences of Pravastatin Isomerization on OATP1B1-Mediated Transport.

ABSTRACT: Pravastatin acid (PVA) can be isomerized to its inactive metabolite 3'α-iso-pravastatin acid (3αPVA) under acidic pH conditions. Previous studies reported interindividual differences in circulating concentrations of PVA and 3αPVA. This study investigated the functional consequences of PVA isomerization on OATP1B1-mediated transport. We characterized 3αPVA inhibition of OATP1B1-mediated PVA uptake into human embryonic kidney 293 cells expressing the four different OATP1B1 proteins (*1a, *1b, *5, and *15). 3αPVA inhibited OATP1B1-mediated PVA uptake in all four OATP1B1 gene products but with lower IC₅₀/K_i values for OATP1B1*5 and *15 than for the reference proteins (*1a and *1b). PVA and 3αPVA were transported by all four OATP1B

SUBMITTER: Wagner JB 

PROVIDER: S-EPMC7589943 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature