The effects of the SLCO2B1 c.1457C > T polymorphism and apple juice on the pharmacokinetics of fexofenadine and midazolam in humans

Pharmacogenet Genomics. 2011 Feb;21(2):84-93. doi: 10.1097/fpc.0b013e32834300cc.


Objective: The objective was to determine the effects of the SLCO2B1 c.1457C> T polymorphism and apple juice on the pharmacokinetics of fexofenadine and midazolam in humans.

Methods: Individuals were divided based on the genotype of SLCO2B1 c.1457C> T (n = 14, c.[1457C]+ c.[= ] 5,c.[1457C]+ c.[1457C> T] 5, and c.[1457C> T]+c.[1457C> T] 4). The oral pharmacokinetics of 60 mg fexofenadine and 5mg midazolam were assessed with water or apple juice (1200 ml/day) in a randomized crossover study. OATP2B1-mediated uptake of fexofenadine and midazolam was evaluated with Xenopus laevis oocyte gene-expression system.

Results: When fexofenadine was administered with water, subjects with c.[1457C> T] allele showed a significant decrease in fexofenadine in the area under the plasma concentration-time curve (AUC) compared with c.[1457C] + c[= ] subjects (1110 ± 347 vs. 1762 ± 542 ng . h/ml, P< 0.05). When administered with apple juice, a significant decrease in the fexofenadine AUC was observed compared with water (1342 ± 519 vs. 284 ± 79.2 ng . h/ml, P < 0.05). The apple juice induced decrease in fexofenadine AUC was significantly lower in subjects carrying the c.[1457C> T] allele. Neither the genotype nor the apple juice showed significant effects on the pharmacokinetics of midazolam except for a marginally significant decrease in Cmax after administration with apple juice. The uptake of fexofenadine by OATP2B1 cRNA-injected oocytes was significantly higher than that by water-injected oocytes. Apple juice, but not midazolam, significantly decreased the uptake of fexofenadine by OATP2B1 cRNA-injected oocytes.

Conclusion: The results suggest that fexofenadine is a substrate of OATP2B1, and the transport function of OATP2B1 is subject to the genotype of SLCO2B1 c.1457C> T and apple juice. It is likely that apple juice has little effect on CYP3A.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Anti-Allergic Agents / administration & dosage
  • Anti-Allergic Agents / pharmacokinetics
  • Area Under Curve
  • Beverages*
  • Biological Transport
  • GABA Modulators / administration & dosage
  • GABA Modulators / pharmacokinetics
  • Humans
  • Male
  • Malus*
  • Midazolam / administration & dosage
  • Midazolam / pharmacokinetics*
  • Organic Anion Transporters / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Terfenadine / administration & dosage
  • Terfenadine / analogs & derivatives*
  • Terfenadine / blood
  • Terfenadine / pharmacokinetics
  • Xenopus laevis
  • Young Adult


  • Anti-Allergic Agents
  • GABA Modulators
  • Organic Anion Transporters
  • SLCO2B1 protein, human
  • Terfenadine
  • fexofenadine
  • Midazolam