ArticlePharmaceutics2021
A Whole-Body Physiologically Based Pharmacokinetic Model Characterizing Interplay of OCTs and MATEs in Intestine, Liver and Kidney to Predict Drug-Drug Interactions of Metformin with Perpetrators.
Article in Pharmaceutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- Clozapine impaired the hypoglycemic effect of metformin by inhibiting hepatic organic cation transporter 1 (OCT1).Acta pharmacologica Sinica · 2026Article
- Pharmacokinetics and Drug Interactions.Pharmaceutics · 2026Article
- Controversial effects of metformin on human physiology and pathophysiology.Frontiers in pharmacology · 2026Review
- Virtual Bioequivalence Assessment and Dissolution Safe Space Exploration for Fixed-Dose Metformin-Glyburide Tablet Using Physiologically Based Biopharmaceutics Modeling.Pharmaceutics · 2025Article
- Applications of PBPK Modeling to Estimate Drug Metabolism and Related ADME Processes in Specific Populations.Pharmaceutics · 2025Review
- Influence of OCT2 gene variants on metformin efficacy in type 2 diabetes: insights into pharmacogenomics and drug interactions.Journal of translational medicine · 2025Review
- Composition of Higher Alcohols in Different Alcoholic Beverages and Their Metabolic Dynamics in Bama Pigs.Foods (Basel, Switzerland) · 2024Article
- No dose adjustment of metformin or substrates of organic cation transporters (OCT)1 and OCT2 and multidrug and toxin extrusion protein (MATE)1/2K with fostemsavir coadministration based on modeling approaches.Pharmacology research & perspectives · 2024Article
- A Review of the Impact of Pharmacogenetics and Metabolomics on the Efficacy of Metformin in Type 2 Diabetes.International journal of medical sciences · 2023Review
- Change of metformin concentrations in the liver as a pharmacological target site of metformin after long-term combined treatment with ginseng berry extract.Frontiers in pharmacology · 2023Article
- Bile duct ligation differently regulates protein expressions of organic cation transporters in intestine, liver and kidney of rats through activation of farnesoid X receptor by cholate and bilirubin.Acta pharmaceutica Sinica. B · 2023Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Transmembrane transport of metformin is highly controlled by transporters including organic cation transporters (OCTs), plasma membrane monoamine transporter (PMAT), and multidrug/toxin extrusions (MATEs). Hepatic OCT1, intestinal OCT3, renal OCT2 on tubule basolateral membrane, and MATE1/2-K on tubule apical membrane coordinately work to control metformin disposition. Drug-drug interactions (DDIs) of metformin occur when co-administrated with perpetrators via inhibiting OCTs or MATEs. We aimed to develop a whole-body physiologically based pharmacokinetic (PBPK) model characterizing interplay of OCTs and MATEs in the intestine, liver, and kidney to predict metformin DDIs with cimetidine, pyrimethamine, trimethoprim, ondansetron, rabeprazole, and verapamil. Simulations showed that co-administration of perpetrators increased plasma exposures to metformin, which were consistent with clinic observations. Sensitivity analysis demonstrated that contributions of the tested factors to metformin DDI with cimetidine are gastrointestinal transit rate > inhibition of renal OCT2 ≈ inhibition of renal MATEs > inhibition of intestinal OCT3 > intestinal pH > inhibition of hepatic OCT1. Individual contributions of transporters to metformin disposition are renal OCT2 ≈ renal MATEs > intestinal OCT3 > hepatic OCT1 > intestinal PMAT. In conclusion, DDIs of metformin with perpetrators are attributed to integrated effects of inhibitions of these transporters.
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