ArticlePharmaceutical research2004
Predicting P-glycoprotein effects on oral absorption: correlation of transport in Caco-2 with drug pharmacokinetics in wild-type and mdr1a(-/-) mice in vivo.
Article in Pharmaceutical research, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Physiologically Based Pharmacokinetic Modeling to Assess Ritonavir-Digoxin Interactions and Recommendations for Co-Administration Regimens.Pharmaceutical research · 2024Article
- Uptake Transporters at the Blood-Brain Barrier and Their Role in Brain Drug Disposition.Pharmaceutics · 2023Review
- Pharmaceutical Formulations with P-Glycoprotein Inhibitory Effect as Promising Approaches for Enhancing Oral Drug Absorption and Bioavailability.Pharmaceutics · 2021Review
- Using Ex Vivo Porcine Jejunum to Identify Membrane Transporter Substrates: A Screening Tool for Early-Stage Drug Development.Biomedicines · 2020Article
- Homology Modeling of the Human P-glycoprotein (ABCB1) and Insights into Ligand Binding through Molecular Docking Studies.International journal of molecular sciences · 2020Article
- Different structures of berberine and five other protoberberine alkaloids that affect P-glycoprotein-mediated efflux capacity.Acta pharmacologica Sinica · 2019Article
- Renal Drug Transporters and Drug Interactions.Clinical pharmacokinetics · 2017Review
- Natural flavonoids silymarin and quercetin improve the brain distribution of co-administered P-gp substrate drugs.SpringerPlus · 2016Article
- Membrane Assays to Characterize Interaction of Drugs with ABCB1.The Journal of membrane biology · 2015Article
- Atovaquone and quinine anti-malarials inhibit ATP binding cassette transporter activity.Malaria journal · 2014Article
- Challenges of using in vitro data for modeling P-glycoprotein efflux in the blood-brain barrier.Pharmaceutical research · 2014Review
- Physiologically based pharmacokinetic modelling of drug penetration across the blood-brain barrier--towards a mechanistic IVIVE-based approach.The AAPS journal · 2013Review
- 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
- Influence of drug transport proteins on the pharmacokinetics and drug interactions of HIV protease inhibitors.Journal of pharmaceutical sciences · 2011Review
- Coexistence of passive and carrier-mediated processes in drug transport.Nature reviews. Drug discovery · 2010Review
- Assessing drug distribution in tissues expressing P-glycoprotein through physiologically based pharmacokinetic modeling: model structure and parameters determination.Theoretical biology & medical modelling · 2009Article
- Metabolic and efflux properties of Caco-2 cells stably transfected with nuclear receptors.Pharmaceutical research · 2006Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeCell-based permeability screens are widely used to identify drug-P-glycoprotein (PGP) interaction in vitro. However, their reliability in predicting the impact of PGP on human drug pharmacokinetics is poorly defined. The aim was to determine whether a quantitative relationship exists between PGP-mediated alterations in Caco-2 permeability and oral pharmacokinetics in mice.
methodsTwo indicators of drug efflux were measured in Caco-2 for a group of 10 compounds, the ratio of A-B and B-A transport (R9B-A/A-B)) and the ratio of A-B transport in the presence and absence of a PGP inhibitor, GF120918 (R(GF)). These data were correlated with ratios of oral plasma levels in either mdr1a(-/-) or mdr1a/1b(-/-) and wild-type mice (R(KO/WT in vivo)) calculated from literature data on these compounds.
resultsA significant, positive correlation (r2 = 0.8, p < 0.01) was observed between RGF and R(KO/WT in vivo). In contrast, R(B-A/A-B), a more commonly used in vitro measure, showed a much weaker correlation with in vivo data (r2 = 0.33, p = 0.11). A strong correlation with R(GF) was also observed after correction of in vivo data for PGP effects on IV clearance.
conclusionThe increase in A-B drug permeability following inhibition of PGP in Caco-2 allows a reasonable prediction of the likely in vivo impact that PGP will have on plasma drug levels after oral administration.
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Registered trials
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