ArticlePharmaceutical research2015
Unstirred Water Layers and the Kinetics of Organic Cation Transport.
Article in Pharmaceutical research, 2015. 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, 22 citations in OpenAlex.
- A toxicokinetic model for gill processes affecting the uptake of perfluoroalkyl acids by freshwater fish.Environmental science. Processes & impacts · 2026Article
- Comparing the Altis RepliGut Organoid System to MDCK Monolayers in Predicting the Oral Absorption of Lenalidomide.Pharmaceutics · 2025Article
- Novel method for kinetic analysis applied to transport by the uniporter OCT2.American journal of physiology. Renal physiology · 2022Article
- Does Oral Apigenin Have Real Potential for a Therapeutic Effect in the Context of Human Gastrointestinal and Other Cancers?Frontiers in pharmacology · 2021Review
- Prediction of Drug Clearance from Enzyme and Transporter Kinetics.Methods in molecular biology (Clifton, N.J.) · 2021Article
- TheEntropy (Basel, Switzerland) · 2020Article
- Kinetic basis of metformin-MPP interactions with organic cation transporter OCT2.American journal of physiology. Renal physiology · 2019Article
- In Silico Prediction of PAMPA Effective Permeability Using a Two-QSAR Approach.International journal of molecular sciences · 2019Article
- The Use of Molecular Descriptors To Model Pharmaceutical Uptake by a Fish Primary Gill Cell Culture Epithelium.Environmental science & technology · 2019Article
- Correlation between Apparent Substrate Affinity and OCT2 Transport Turnover.The Journal of pharmacology and experimental therapeutics · 2017Article
- Recent advances in understanding hepatic drug transport.F1000Research · 2016Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeUnstirred water layers (UWLs) present an unavoidable complication to the measurement of transport kinetics in cultured cells, and the high rates of transport achieved by overexpressing heterologous transporters exacerbate the UWL effect. This study examined the correlation between measured Jmax and Kt values and the effect of manipulating UWL thickness or transport Jmax on the accuracy of experimentally determined kinetics of the multidrug transporters, OCT2 and MATE1.
methodsTransport of TEA and MPP was measured in CHO cells that stably expressed human OCT2 or MATE1. UWL thickness was manipulated by vigorous reciprocal shaking. Several methods were used to manipulate maximal transport rates.
resultsVigorous stirring stimulated uptake of OCT2-mediated transport by decreasing apparent Kt (Ktapp) values. Systematic reduction in transport rates was correlated with reduction in Ktapp values. The slope of these relationships indicated a 1500 μm UWL in multiwell plates. Reducing the influence of UWLs (by decreasing either their thickness or the Jmax of substrate transport) reduced Ktapp by 2-fold to >10-fold.
conclusionsFailure to take into account the presence of UWLs in experiments using cultured cells to measure transport kinetics can result in significant underestimates of the apparent affinity of multidrug transporters for substrates.
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