ArticlePharmaceutical research2003
pH-dependent bidirectional transport of weakly basic drugs across Caco-2 monolayers: implications for drug-drug interactions.
Article in Pharmaceutical research, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed.
- Examining the Use of a Mechanistic Model to Generate an In Vivo/In Vitro Correlation: Journey Through a Thought Process.The AAPS journal · 2016Trial
- Assessment of In Vivo Clinical Product Performance of a Weak Basic Drug by Integration of In Vitro Dissolution Tests and Physiologically Based Absorption Modeling.The AAPS journal · 2015Trial
- Classifying Effluxable Versus Non-Effluxable Compounds Using a Permeability Threshold Based on Fundamental Energy Constraints.Pharmaceutics · 2025Article
- Exploring Experimental and Statistical Approaches to Control Oversensitivity of In Vitro Permeability to Excipient Effects.Pharmaceutics · 2025Article
- Quantitative in vitro-to-in vivo extrapolation of human adrenergic and trace amine-associated receptor 1 potencies of pre-workout supplement ingredients using physiologically based kinetic modelling-based reverse dosimetry.Archives of toxicology · 2025Article
- Mechanistic studies on pH-permeability relationships: Impact of the membrane polar headgroup region on pKa.International journal of pharmaceutics · 2025Article
- The pH-dependence of efflux ratios determined with bidirectional transport assays across cellular monolayers.International journal of pharmaceutics: X · 2024Article
- Improving the Accuracy of Permeability Data to Gain Predictive Power: Assessing Sources of Variability in Assays Using Cell Monolayers.Membranes · 2024Review
- Structural insights into human organic cation transporter 1 transport and inhibition.Cell discovery · 2024Article
- Challenges in Permeability Assessment for Oral Drug Product Development.Pharmaceutics · 2023Review
- Regulation of Transporters for Organic Cations by High Glucose.International journal of molecular sciences · 2023Article
- Molecular basis of polyspecific drug and xenobiotic recognition by OCT1 and OCT2.Nature structural & molecular biology · 2023Article
- Molecular basis of polyspecific drug binding and transport by OCT1 and OCT2.bioRxiv : the preprint server for biology · 2023Article
- An AIE-Active probe for detection and bioimaging of pH values based on lactone hydrolysis reaction.Journal of fluorescence · 2022Article
- Transport Turnover Rates for Human OCT2 and MATE1 Expressed in Chinese Hamster Ovary Cells.International journal of molecular sciences · 2022Article
- Cationic Compounds with SARS-CoV-2 Antiviral Activity and Their Interaction with Organic Cation Transporter/Multidrug and Toxin Extruder Secretory Transporters.The Journal of pharmacology and experimental therapeutics · 2021Article
- Transport of Drugs and Endogenous Compounds Mediated by Human OCT1: Studies in Single- and Double-Transfected Cell Models.Frontiers in pharmacology · 2021Review
- Drug-Drug Interactions at Organic Cation Transporter 1.Frontiers in pharmacology · 2021Review
- Organic Cation Transporters in Human Physiology, Pharmacology, and Toxicology.International journal of molecular sciences · 2020Review
- Insight into the Anticancer Activity of Copper(II) 5-Methylenetrimethylammonium-Thiosemicarbazonates and Their Interaction with Organic Cation Transporters.Biomolecules · 2020Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe purpose of this study was to investigate the pH-dependent passive and active transport of weakly basic drugs across the human intestinal epithelium.
methodsThe bidirectional pH-dependent transport of weak bases was studied in Caco-2 cell monolayers in the physiologic pH range of the gastrointestinal tract.
resultsA net secretion of atenolol and metoprolol was observed when a pH gradient was applied. However, the bidirectional transport of both compounds was equal in the nongradient system. Hence, at lower apical than basolateral pH a change in passive transport caused by an imbalance in the concentration of the uncharged drug species resulted in a "false" asymmetry (efflux ratio). Furthermore, a mixture of pH-dependent passive and active efflux was found for the P-glycoprotein (P-gp, MDR1, ABCB1) substrates, talinolol and quinidine, but not for the neutral drug, digoxin. However, the clinically important digoxin-quinidine interaction depended on the presence of a pH gradient. Hence, the degree of interaction depends on the amount of quinidine available at the binding site of the P-gp.
conclusionsActive efflux of weak bases can only be accounted for when the fraction of unionized drug species is equal in all compartments because the transport is biased by a pH-dependent passive component. However, this component may take part in vivo and contribute to drug-drug interactions involving P-gp.
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Registered trials
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