Maraviroc is a substrate for OATP1B1 in vitro and maraviroc plasma concentrations are influenced by SLCO1B1 521 T>C polymorphism

Pharmacogenet Genomics. 2010 Dec;20(12):759-65. doi: 10.1097/FPC.0b013e3283402efb.


Background: Organic anion transporting polypeptides (OATPs) are emerging as major determinants of pharmacokinetics for numerous drugs, with the 1B1 isoform-mediating hepatic uptake. The 521 T>C polymorphism has been correlated earlier with higher plasma concentrations of several drugs and the aim of this study was to determine whether this polymorphism influences trough concentrations of maraviroc.

Methods: The uptake of maraviroc by OATP1B1 was assessed using a heterologous Xenopus laevis oocyte expression system and quantified using a novel liquid chromatography-mass spectrometry method. Regression analyses were conducted to identify factors associated with maraviroc Ctrough in 59 patients treated with maraviroc at 150, 300, or 600 mg twice daily.

Results: Maraviroc was identified as a substrate for OATP1B1 with a Km of 33.9 μmol/l. A dose of 600 mg of etravirine or efavirenz [odds ratio (OR) = 0.22, 95% confidence interval (95% CI): 0.06-0.76; P = 0.016] and SLCO1B1 521 heterozygosity were both associated with maraviroc Ctrough, above the suggested target concentration of 50 ng/ml (OR = 20.3, 95% CI: 2.2-182; P = 0.007).

Conclusion: These findings show the importance of OATP1B1 for variability in maraviroc pharmacokinetics. Furthermore, the SLCO1B1 521 T>C polymorphism maybe useful in predicting higher plasma concentrations but these data should be confirmed before prospective clinical studies to define the clinical usefulness.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Animals
  • Biological Transport / drug effects
  • Chromatography, Liquid
  • Cyclohexanes / blood*
  • Cyclohexanes / pharmacology
  • Dose-Response Relationship, Drug
  • Female
  • Genetic Association Studies
  • Genotype
  • Humans
  • Liver-Specific Organic Anion Transporter 1
  • Male
  • Maraviroc
  • Mass Spectrometry
  • Middle Aged
  • Oocytes / drug effects
  • Oocytes / metabolism
  • Organic Anion Transporters / genetics*
  • Organic Anion Transporters / metabolism*
  • Polymorphism, Single Nucleotide / genetics*
  • Reproducibility of Results
  • Substrate Specificity / drug effects
  • Triazoles / blood*
  • Triazoles / pharmacology
  • Xenopus laevis


  • Cyclohexanes
  • Liver-Specific Organic Anion Transporter 1
  • Organic Anion Transporters
  • SLCO1B1 protein, human
  • Triazoles
  • Maraviroc