ArticlePloS one2017
Effects of genetic polymorphisms on the OCT1 and OCT2-mediated uptake of ranitidine.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 56 citations in OpenAlex.
- Sex-Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans.Clinical pharmacology and therapeutics · 2025Trial
- Feed-Forward Deep Neural Networks Predict Substrate-Specific Effects of Transporter Variants to Explain Drug Response Variability.Clinical and translational science · 2026Article
- Quantitative Analysis of the Effect of Gastrointestinal Water Dynamics on Oral Drug Absorption using a Physiologically Based Integrated Liquid and Intestinal Absorption Drug (ILIAD) Pharmacokinetic Model.Pharmaceutical research · 2026Article
- Canine Mdr1 Knockout MDCK Cells Reliably Estimate Human Small Intestinal Permeability (Molecular pharmaceutics · 2025Article
- Pharmacogenetics and Molecular Ancestry ofPharmaceuticals (Basel, Switzerland) · 2025Article
- Research Methods and New Advances in Drug-Drug Interactions Mediated by Renal Transporters.Molecules (Basel, Switzerland) · 2023Review
- Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients.Acta pharmaceutica Sinica. B · 2023Review
- Quantitative Proteomics in Translational Absorption, Distribution, Metabolism, and Excretion and Precision Medicine.Pharmacological reviews · 2022Review
- Cloning and Functional Characterization of Dog OCT1 and OCT2: Another Step in Exploring Species Differences in Organic Cation Transporters.International journal of molecular sciences · 2022Article
- Relationships between Inhibition, Transport and Enhanced Transport via the Organic Cation Transporter 1.International journal of molecular sciences · 2022Article
- Overview of Drug Transporters in Human Placenta.International journal of molecular sciences · 2021Review
- OCT1 Polyspecificity-Friend or Foe?Frontiers in pharmacology · 2021Article
- Transport of Drugs and Endogenous Compounds Mediated by Human OCT1: Studies in Single- and Double-Transfected Cell Models.Frontiers in pharmacology · 2021Review
- Substrates and Inhibitors of Organic Cation Transporters (OCTs) and Plasma Membrane Monoamine Transporter (PMAT) and Therapeutic Implications.Handbook of experimental pharmacology · 2021Article
- Organic Cation Transporter 1 an Intestinal Uptake Transporter: Fact or Fiction?Frontiers in pharmacology · 2021Review
- Drug-Drug Interactions at Organic Cation Transporter 1.Frontiers in pharmacology · 2021Review
- Expansion of Knowledge on OCT1 Variant ActivityFrontiers in pharmacology · 2021Article
- Functional and Pharmacological Comparison of Human, Mouse, and Rat Organic Cation Transporter 1 toward Drug and Pesticide Interaction.International journal of molecular sciences · 2020Article
- Molecular and cellular physiology of organic cation transporter 2.American journal of physiology. Renal physiology · 2019Review
- Transporters in the Mammary Gland-Contribution to Presence of Nutrients and Drugs into Milk.Nutrients · 2019Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRanitidine (Zantac®) is a H2-receptor antagonist commonly used for the treatment of acid-related gastrointestinal diseases. Ranitidine was reported to be a substrate of the organic cation transporters OCT1 and OCT2. The hepatic transporter OCT1 is highly genetically variable. Twelve major alleles confer partial or complete loss of OCT1 activity. The effects of these polymorphisms are highly substrate-specific and therefore difficult to predict. The renal transporter OCT2 has a common polymorphism, Ala270Ser, which was reported to affect OCT2 activity.
aimIn this study we analyzed the effects of genetic polymorphisms in OCT1 and OCT2 on the uptake of ranitidine and on its potency to inhibit uptake of other drugs. METHODS AND
resultsWe characterized ranitidine uptake using HEK293 and CHO cells stably transfected to overexpress wild type OCT1, OCT2, or their naturally occurring allelic variants. Ranitidine was transported by wild-type OCT1 with a Km of 62.9 μM and a vmax of 1125 pmol/min/mg protein. Alleles OCT1*5, *6, *12, and *13 completely lacked ranitidine uptake. Alleles OCT1*2, *3, *4, and *10 had vmax values decreased by more than 50%. In contrast, OCT1*8 showed an increase of vmax by 25%. The effects of OCT1 alleles on ranitidine uptake strongly correlated with the effects on morphine uptake suggesting common interaction mechanisms of both drugs with OCT1. Ranitidine inhibited the OCT1-mediated uptake of metformin and morphine at clinically relevant concentrations. The inhibitory potency for morphine uptake was affected by the OCT1*2 allele. OCT2 showed only a limited uptake of ranitidine that was not significantly affected by the Ala270Ser polymorphism.
conclusionsWe confirmed ranitidine as an OCT1 substrate and demonstrated that common genetic polymorphisms in OCT1 strongly affect ranitidine uptake and modulate ranitidine's potential to cause drug-drug interactions. The effects of the frequent OCT1 polymorphisms on ranitidine pharmacokinetics in humans remain to be analyzed.
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