OATP1B1 polymorphism as a determinant of erythromycin disposition.

ABSTRACT: Previous studies have demonstrated that the pharmacokinetic profile of erythromycin, a probe for CYP3A4 activity, is affected by inhibitors or inducers of hepatic solute carriers. We hypothesized that these interactions are mediated by OATP1B1 (gene symbol, SLCO1B1), a polypeptide expressed on the basolateral surface of hepatocytes. Using stably transfected Flp-In T-Rex293 cells, erythromycin was found to be a substrate for OATP1B1*1A (wild type) with a Michaelis-Menten constant of ~13 µmol/l, and that its transport was reduced by ~50% in cells expressing OATP1B1*5 (V174A). Deficiency of the ortholog transporter Oatp1b2 in mice was associated with a 52% decrease in the metabolic rate of erythromycin (P = 0.000043). In line with these observations, in humans the c.521T>C variant in SLCO1B1

SUBMITTER: Lancaster CS 

PROVIDER: S-EPMC3478421 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature