OATP1B1 polymorphism as a determinant of erythromycin disposition

Clin Pharmacol Ther. 2012 Nov;92(5):642-50. doi: 10.1038/clpt.2012.106. Epub 2012 Sep 19.


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 (rs4149056), encoding OATP1B1*5, was associated with a decline in erythromycin metabolism (P = 0.0072). These results suggest that impairment of OATP1B1 function can alter erythromycin metabolism, independent of changes in CYP3A4 activity.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Anti-Bacterial Agents / pharmacokinetics*
  • Biological Transport
  • Cell Line
  • Cytochrome P-450 CYP3A / metabolism
  • Erythromycin / pharmacokinetics*
  • Female
  • Humans
  • Liver-Specific Organic Anion Transporter 1
  • Male
  • Mice
  • Mice, Knockout
  • Middle Aged
  • Organic Anion Transporters / genetics*
  • Organic Anion Transporters / metabolism
  • Organic Anion Transporters, Sodium-Independent / genetics*
  • Polymorphism, Genetic


  • Anti-Bacterial Agents
  • Liver-Specific Organic Anion Transporter 1
  • Organic Anion Transporters
  • Organic Anion Transporters, Sodium-Independent
  • SLCO1B1 protein, human
  • Slco1b2 protein, mouse
  • Erythromycin
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human