Comparison of the transport kinetics of fexofenadine and its pH dependency among OATP1A2 genetic variants

Hongye Han, Takeshi Akiyoshi, Tokio Morita, Hiroki Kataoka, Kazuhiro Katayama, Kodai Yajima, Ayuko Imaoka, Hisakazu Ohtani

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Little is known about the influence of non-synonymous genetic variations in the organic anion-transporting polypeptide (OATP) 1A2 on the transport kinetics of its substrate fexofenadine. Moreover, the pH-dependency of fexofenadine uptake also remains unclear. This study aimed to evaluate the effects of genetic variants (Ile13Thr, Asn128Tyr, Glu172Asp, Ala187Thr, and Thr668Ser) on the OATP1A2-mediated uptake of fexofenadine at pH 6.3 and 7.4 and compare the pH dependency of OATP1A2-mediated uptake of fexofenadine and estrone 3-sulfate. The uptake clearances of 0.3 μM and 300 μM fexofenadine were compared with those of 0.3 μM and 300 μM estrone 3-sulfate at pH 6.3 and 7.4. Among the six variants examined, the Thr668Ser variant showed the highest fexofenadine uptake clearance (Vmax/Km); i.e., 4.53- and 6.28-fold higher uptake clearance than the wild type at pH 6.3 and 7.4, respectively. All variants exhibited significantly higher fexofenadine uptake at pH 6.3 than at pH 7.4. Compared with estrone 3-sulfate uptake, the uptake of 0.3 μM fexofenadine was less sensitive to pH. Our findings suggest that genetic variations in OATP1A2 may lead to altered intestinal absorption of fexofenadine, such as increased absorption in subjects bearing the Thr668Ser variant, which showed higher uptake activity.

Original languageEnglish
Article number100470
JournalDrug Metabolism And Pharmacokinetics
Publication statusPublished - 2022 Dec


  • Amino acid substitution
  • Estrone 3-sulfate
  • Intestinal absorption
  • Organic anion-transporting polypeptide 1A2
  • Single nucleotide polymorphism
  • pH-dependent uptake

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)


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