ArticlePharmaceutical research2014
Substrate- and dose-dependent drug interactions with grapefruit juice caused by multiple binding sites on OATP2B1.
Article in Pharmaceutical research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 61 citations in OpenAlex.
- Exposure of Fexofenadine, but Not Pseudoephedrine, Is Markedly Decreased by Green Tea Extract in Healthy Volunteers.Clinical pharmacology and therapeutics · 2022Trial
- The Pharmacokinetic Exposure to Fexofenadine is Volume-Dependently Reduced in Healthy Subjects Following Oral Administration With Apple Juice.Clinical and translational science · 2016Trial
- Physiologically Based Pharmacokinetic (PBPK) Modeling of Oral Drug Absorption for Integrating Nonclinical Data into Human Pharmacokinetic Predictions.The AAPS journal · 2026Review
- A Mechanistic Physiologically Based Pharmacokinetic (PBPK) modeling approach for fexofenadine: predictive pharmacokinetic insights in humans.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2025Article
- Effect of Organic Anion Transporting Polypeptide 1B1 on Plasma Concentration Dynamics of Clozapine in Patients with Treatment-Resistant Schizophrenia.International journal of molecular sciences · 2024Article
- Conversion of Olmesartan to Olmesartan Medoxomil, A Prodrug that Improves Intestinal Absorption, Confers Substrate Recognition by OATP2B1.Pharmaceutical research · 2024Article
- Investigating the interactions of flavonoids with human OATP2B1: inhibition assay, ICRSC medicinal chemistry · 2023Article
- Evaluation of the Potential for Cytochrome P450 and Transporter-Mediated Drug-Drug Interactions for Cilofexor, a Selective Nonsteroidal Farnesoid X Receptor (FXR) Agonist.Clinical pharmacokinetics · 2023Article
- Network Analysis of the Herb-Drug Interactions of Citrus Herbs Inspired by the "Grapefruit Juice Effect".ACS omega · 2022Article
- Role of Uptake Transporters OAT4, OATP2A1, and OATP1A2 in Human Placental Bio-disposition of Pravastatin.Journal of pharmaceutical sciences · 2022Article
- Uptake Pathway of Apple-derived Nanoparticle by Intestinal Cells to Deliver its Cargo.Pharmaceutical research · 2021Article
- Investigation of Fluorescent Substrates and Substrate-Dependent Interactions of a Drug Transporter Organic Anion Transporting Polypeptide 2B1 (OATP2B1).Pharmaceutical research · 2020Article
- Stimulatory effect on the transport mediated by organic anion transporting polypeptide 2B1.Asian journal of pharmaceutical sciences · 2020Review
- Transporters in Drug Development: 2018 ITC Recommendations for Transporters of Emerging Clinical Importance.Clinical pharmacology and therapeutics · 2018Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeOATP2B1-mediated grapefruit juice (GFJ)-drug interactions are substrate-dependent; for example, GFJ ingestion significantly reduces bioavailability of fexofenadine, but not pravastatin. In the present study, we aimed to establish whether this observation can be explained by the presence of multiple binding sites (MBS) on OATP2B1.
methodsOATP2B1-mediated drug uptake was evaluated using a Xenopus oocyte expression system. Drug concentration was quantified by LC/MS/MS analysis.
resultsOATP2B1-mediated uptake of pravastatin and fexofenadine exhibited biphasic saturation kinetics, indicating the presence of MBS on OATP2B1. GFJ strongly inhibited pravastatin uptake mediated by the high-affinity site on OATP2B1, while no significant inhibition of the low-affinity site was observed. In contrast, high-affinity transport of fexofenadine was only modestly inhibited by GFJ, while significant inhibition of the low-affinity site was observed. Contribution analysis indicated that both drugs are transported via the low-affinity site on OATP2B1 at therapeutically relevant concentrations. These findings indicate that only fexofenadine is expected to interact with GFJ on OATP2B1 at therapeutic concentrations, in accordance with the clinical observations.
conclusionSubstrate- and dose-dependent GFJ-drug interactions mediated by OATP2B1 might be explained in terms of the presence of MBS: interaction occurs only when drug and GFJ components share the same binding site on OATP2B1.
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