ArticlePharmaceutical research2006
Intestinal absorptive transport of the hydrophilic cation ranitidine: a kinetic modeling approach to elucidate the role of uptake and efflux transporters and paracellular vs. transcellular transport in Caco-2 cells.
Article in Pharmaceutical research, 2006. 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, 58 citations in OpenAlex.
- Polyethylene glycol 400 enhances the bioavailability of a BCS class III drug (ranitidine) in male subjects but not females.Pharmaceutical research · 2008Trial
- Structure and function of neurovascular unit in arterial hypertension.Frontiers in molecular neuroscience · 2025Review
- A Critical Overview of the Biological Effects of Excipients (Part I): Impact on Gastrointestinal Absorption.The AAPS journal · 2022Review
- Review
- Review
- In vitro transport characteristics of EFdA, a novel nucleoside reverse transcriptase inhibitor using Caco-2 and MDCKII cell monolayers.European journal of pharmacology · 2014Article
- Computational approaches to analyse and predict small molecule transport and distribution at cellular and subcellular levels.Biopharmaceutics & drug disposition · 2014Review
- Organic cation transporter 1 (OCT1/mOct1) is localized in the apical membrane of Caco-2 cell monolayers and enterocytes.Molecular pharmacology · 2013Article
- Drug discovery and regulatory considerations for improving in silico and in vitro predictions that use Caco-2 as a surrogate for human intestinal permeability measurements.The AAPS journal · 2013Article
- Development and evaluation of an in vitro vaginal model for assessment of drug's biopharmaceutical properties: curcumin.AAPS PharmSciTech · 2012Article
- Safe and effective permeation enhancers for oral drug delivery.Pharmaceutical research · 2008Article
- Mechanistic analysis of chemical permeation enhancers for oral drug delivery.Pharmaceutical research · 2008Article
- Predicting drug disposition, absorption/elimination/transporter interplay and the role of food on drug absorption.Advanced drug delivery reviews · 2008Review
- Saturable absorptive transport of the hydrophilic organic cation ranitidine in Caco-2 cells: role of pH-dependent organic cation uptake system and P-glycoprotein.Pharmaceutical research · 2006Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe mechanism of intestinal drug transport for hydrophilic cations such as ranitidine is complex, and evidence suggests a role for carrier-mediated apical (AP) uptake and saturable paracellular mechanisms in their overall absorptive transport. The purpose of this study was to develop a model capable of describing the kinetics of cellular accumulation and transport of ranitidine in Caco-2 cells, and to assess the relative contribution of the transcellular and paracellular routes toward overall ranitidine transport.
methodsCellular accumulation and absorptive transport of ranitidine were determined in the absence or presence of uptake and efflux inhibitors and as a function of concentration over 60 min in Caco-2 cells. A three-compartment model was developed, and parameter estimates were utilized to assess the expected relative contribution from transcellular and paracellular transport.
resultsUnder all conditions, ranitidine absorptive transport consisted of significant transcellular and paracellular components. Inhibition of P-glycoprotein decreased the AP efflux rate constant (k21) and increased the relative contribution of the transcellular transport pathway. In the presence of quinidine, both the AP uptake rate constant (k12) and k21 decreased, resulting in a predominantly paracellular contribution to ranitidine transport. Increasing the ranitidine donor concentration decreased k12 and the paracellular rate constant (k13). No significant changes were observed in the relative contribution of the paracellular and transcellular routes as a function of ranitidine concentration.
conclusionsThese results suggest the importance of uptake and efflux transporters as determinants of the relative contribution of transcellular and paracellular transport for ranitidine, and provide evidence supporting a concentration-dependent paracellular transport mechanism. The modeling approach developed here may also be useful in estimating the relative contribution of paracellular and transcellular transport for a wide array of drugs expected to utilize both pathways.
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