ArticleBritish journal of pharmacology2002
Resolution of P-glycoprotein and non-P-glycoprotein effects on drug permeability using intestinal tissues from mdr1a (-/-) mice.
Article in British journal of pharmacology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 51 citations in OpenAlex.
- Therapeutic Approaches Interfering with Nuclear Localization Signals: An Emerging Strategy for CNS-Related Diseases.Current neuropharmacology · 2026Review
- Experimental and Computational Methods to Assess Central Nervous System Penetration of Small Molecules.Molecules (Basel, Switzerland) · 2024Review
- IPEC-J2 rMdr1a, a New Cell Line with Functional Expression of Rat P-glycoprotein Encoded by Rat Mdr1a for Drug Screening Purposes.Pharmaceutics · 2020Article
- Article
- Changes of Absorptive and Secretory Transporting System of (1 → 3) β-D-glucan Based on Efflux Transporter in Indomethacin-induced Rat.European journal of drug metabolism and pharmacokinetics · 2015Article
- Oral treatment with etoposide in small cell lung cancer - dilemmas and solutions.Radiology and oncology · 2013Article
- Overcoming drug resistance by regulating nuclear receptors.Advanced drug delivery reviews · 2010Review
- 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
- Species difference in intestinal absorption mechanism of etoposide and digoxin between cynomolgus monkey and rat.Pharmaceutical research · 2008Article
- Anchoring junctions as drug targets: role in contraceptive development.Pharmacological reviews · 2008Review
- Molecular evidence and functional expression of a novel drug efflux pump (ABCC2) in human corneal epithelium and rabbit cornea and its role in ocular drug efflux.International journal of pharmaceutics · 2007Article
- Predicting P-glycoprotein effects on oral absorption: correlation of transport in Caco-2 with drug pharmacokinetics in wild-type and mdr1a(-/-) mice in vivo.Pharmaceutical research · 2004Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
1. Intestinal xenobiotic transporters are a significant barrier to the absorption of many orally administered drugs. P-glycoprotein (PGP) is the best known, but several others, including members of the multidrug resistance-associated protein (MRP) family, are also expressed. Definitive information on their precise effect on intestinal drug permeability is scarce due to a lack of specific inhibitors and the difficulty of studying non-PGP activity in the presence of high PGP expression. 2. We have investigated the in vitro use of intestinal tissues from PGP knockout (mdr1a (-/-)) mice as a tool for dissecting the mechanisms of intestinal drug efflux. The permeability characteristics of digoxin (DIG), paclitaxel (TAX) and etoposide (ETOP) were measured in ileum from mdr1a (-/-) and wild-type (FVB) mice mounted in Ussing chambers. 3. DIG and TAX exhibited marked efflux across FVB tissues (B-A : A-B apparent permeability (P(app)) ratio 10 and 17 respectively) which was absent in mdr1a (-/-) tissues, confirming that PGP is the sole route of intestinal efflux for these compounds. The A-B P(app) of both compounds was 3 - 5 fold higher in mdr1a (-/-) than in FVB. 4. Polarized transport of ETOP in FVB tissues was reduced but not abolished in mdr1a (-/-) tissues. Residual ETOP efflux in mdr1a (-/-) tissues was abolished by the MRP inhibitor MK571, indicating involvement of both PGP and MRP. 5. MK571 abolished calcein efflux in mdr1a (-/-) tissues, while quinidine had no parallel effect in FVB tissues, suggesting involvement of MRP but not PGP. 6. Tissues from mdr1a (-/-) mice provide a novel approach for investigating the influence of PGP ablation on intestinal permeability and for resolving PGP and non-PGP mechanisms that modulate drug permeability.
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