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Potential Drug Interactions Mediated by Renal Organic Anion Transporter OATP4C1

Toshihiro Sato1, Eikan Mishima1, Nariyasu Mano1

  • 1Department of Pharmaceutical Sciences, Tohoku University Hospital (T.S., N.M., H.Y.); Division of Nephrology, Endocrinology, and Vascular Medicine, Graduate School of Medicine (E.M., T.A.); Division of Medical Science, Graduate School of Biomedical Engineering (T.A.); Department of Clinical Biology and Hormonal Regulation, Graduate School of Medicine (T.A.), Tohoku University, Sendai, Japan.

The Journal of Pharmacology and Experimental Therapeutics
|May 28, 2017
PubMed

Insights

Organic anion-transporting polypeptide 4C1 (OATP4C1) plays a key role in drug excretion. This study identified 10 drugs that strongly inhibit OATP4C1, with ritonavir showing the highest potential for clinical drug interactions.

Area of Science:

  • Pharmacology
  • Drug Metabolism and Transporter Studies

Background:

  • Organic anion-transporting polypeptide 4C1 (OATP4C1) is crucial for renal excretion of drugs and endogenous compounds.
  • Understanding OATP4C1's pharmacologic profile is essential for safe and effective clinical drug therapy and development.
  • Previous research highlighted OATP4C1's physiological and pathological roles, but its drug interaction potential remained largely uncharacterized.

Purpose of the Study:

  • To investigate and clarify drug interactions mediated by OATP4C1.
  • To screen a range of clinically relevant drugs for their inhibitory effects on OATP4C1.
  • To assess the clinical significance of observed OATP4C1-mediated drug interactions.

Main Methods:

  • Screening of 53 common therapeutic drugs using an OATP4C1-expressing cell system.
  • Evaluation of IC50 values for drugs inhibiting OATP4C1-mediated triiodothyronine transport.
  • Calculation of drug-drug interaction (DDI) indices to predict clinical relevance.

Main Results:

  • Twenty-two out of 53 screened drugs inhibited OATP4C1-mediated transport.
  • Ten drugs, including ritonavir, nicardipine, and verapamil, strongly inhibited OATP4C1.
  • Ritonavir exhibited the highest DDI index (1.9), indicating a significant potential for clinical drug interactions via OATP4C1.

Conclusions:

  • OATP4C1 is a significant transporter involved in drug interactions.
  • Ritonavir's high DDI index suggests a substantial risk of clinical drug interactions.
  • These findings provide crucial insights for optimizing drug therapy and development involving OATP4C1.

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