Abstract
The success of an oral drug route administration depends on many factors that interfere in its bioavailability, therapeutic efficacy and clinical safety. In human cells, ATP-dependent efflux transporter proteins, such as P-glycoprotein (P-gp), BCRP and MRP2, reduce the absorption of drugs. A tiered approach chosen to evaluate drugs as substrates or inhibitors of efflux pumps, particularly P-gp, should be carefully selected, since each study method has advantages and intrinsic limitations to their processes. Depending on the adopted study conditions, the results may not correspond to the real characteristics of the drug regarding to its modulation by specific efflux proteins. This mini-review aims at summarizing the role of P-gp in the drugs oral absorption and correlating some of the most used permeability methods to determine the drug condition as P-gp substrate. Studies about P-gp have shown that it is a dynamic protein, facilitating secretion of endogenous compounds, as aldosterone, and protecting cells against xenobiotics. Different efflux assays are employed to evaluate drugs as P-gp substrates. In an initial planning, MDCK-MDR1 tend to be the chosen method for efflux studies due its ability of express P-gp, followed by studies conducted in Caco-2 models. However, it is necessary to evaluate the advantages and disadvantages of each method to generate sound results and to set the correlation in vitro x in situ x in vivo.
Keywords: Caco-2, drug permeability, efflux, ex vivo, in situ, in vitro, MDCK, MDCK-MDR1, P-glycoprotein.
Mini-Reviews in Medicinal Chemistry
Title:Evaluating Potential P-gp Substrates: Main Aspects to Choose the Adequate Permeability Model for Assessing Gastrointestinal Drug Absorption
Volume: 15 Issue: 10
Author(s): Joao Batista da Silva Junior, Thaisa Marinho Dezani, Andre Bersani Dezani and Cristina Helena dos Reis Serra
Affiliation:
Keywords: Caco-2, drug permeability, efflux, ex vivo, in situ, in vitro, MDCK, MDCK-MDR1, P-glycoprotein.
Abstract: The success of an oral drug route administration depends on many factors that interfere in its bioavailability, therapeutic efficacy and clinical safety. In human cells, ATP-dependent efflux transporter proteins, such as P-glycoprotein (P-gp), BCRP and MRP2, reduce the absorption of drugs. A tiered approach chosen to evaluate drugs as substrates or inhibitors of efflux pumps, particularly P-gp, should be carefully selected, since each study method has advantages and intrinsic limitations to their processes. Depending on the adopted study conditions, the results may not correspond to the real characteristics of the drug regarding to its modulation by specific efflux proteins. This mini-review aims at summarizing the role of P-gp in the drugs oral absorption and correlating some of the most used permeability methods to determine the drug condition as P-gp substrate. Studies about P-gp have shown that it is a dynamic protein, facilitating secretion of endogenous compounds, as aldosterone, and protecting cells against xenobiotics. Different efflux assays are employed to evaluate drugs as P-gp substrates. In an initial planning, MDCK-MDR1 tend to be the chosen method for efflux studies due its ability of express P-gp, followed by studies conducted in Caco-2 models. However, it is necessary to evaluate the advantages and disadvantages of each method to generate sound results and to set the correlation in vitro x in situ x in vivo.
Export Options
About this article
Cite this article as:
da Silva Junior Batista Joao, Dezani Marinho Thaisa, Dezani Bersani Andre and dos Reis Serra Helena Cristina, Evaluating Potential P-gp Substrates: Main Aspects to Choose the Adequate Permeability Model for Assessing Gastrointestinal Drug Absorption, Mini-Reviews in Medicinal Chemistry 2015; 15 (10) . https://dx.doi.org/10.2174/1389557515666150511152705
DOI https://dx.doi.org/10.2174/1389557515666150511152705 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Mitochondria as a Therapeutic Target in Metabolic Disorders
Mitochondria are the primary site of adenosine triphosphate (ATP) production in mammalian cells. Moreover, these organelles are an important source of reactive oxygen and nitrogen species in virtually any nucleated cell type. The modulation of a myriad of cellular signaling pathways depends on the mitochondrial physiology. Mitochondrial dysfunction is observed ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
VEGF/VEGFR Pathway Inhibitors as Anti-Angiogenic Agents: Present and Future
Current Cancer Drug Targets Targeting Human Telomerase in Cancer Therapy
Current Medicinal Chemistry - Anti-Cancer Agents Fibroblast Growth Factor Receptor Signaling in Cancer Biology and Treatment
Current Signal Transduction Therapy Nanoparticles of Biodegradable Polymers for Clinical Administration of Paclitaxel
Current Medicinal Chemistry Allosteric Modulation of Protease-Activated Receptor Signaling
Mini-Reviews in Medicinal Chemistry In Vivo Inhibition of the Estrogen Sulfatase Enzyme and Growth of DMBA-Induced Mammary Tumors by Melatonin
Current Cancer Drug Targets Immune Modulation of Asian Folk Herbal Medicines and Related Chemical Components for Cancer Management
Current Medicinal Chemistry Multiple Roles of Annexin A2 in Post-Transcriptional Regulation of Gene Expressio
Current Protein & Peptide Science Disintegrins from Snake Venoms and their Applications in Cancer Research and Therapy
Current Protein & Peptide Science Effects of Physical Exercise on Depressive Symptoms and Biomarkers in Depression
CNS & Neurological Disorders - Drug Targets Strategies for Targeting the Multidrug Resistance-1 (MDR1)/P-gp Transporter in Human Malignancies
Current Cancer Drug Targets Plant Troponoids: Chemistry, Biological Activity, and Biosynthesis
Current Medicinal Chemistry Polymeric Nano-Encapsulation of Curcumin Enhances its Anti-Cancer Activity in Breast (MDA-MB231) and Lung (A549) Cancer Cells Through Reduction in Expression of HIF-1α and Nuclear p65 (Rel A)
Current Drug Delivery The Interaction of GLUT1 and FOXM1 Leads to a Poor Prognosis in Colorectal Cancer
Anti-Cancer Agents in Medicinal Chemistry Contribution of Magnetic Resonance Imaging in Determining Lumpectomy Cavity in Breast Radiotherapy
Current Medical Imaging Equol is Neuroprotective During Focal Cerebral Ischemia and Reperfusion that Involves p-Src and gp91<sup>phox</sup>
Current Neurovascular Research Apoptosis: Mediator Molecules, Interplay with Other Cell Death Processes and Therapeutic Potentials
Current Pharmaceutical Biotechnology CRM1-Mediated Nuclear Export of Proteins and Drug Resistance in Cancer
Current Medicinal Chemistry Hydrogen Sulfide Prevents Hyperoxia-induced Lung Injury by Downregulating Reactive Oxygen Species Formation and Angiopoietin-2 Release
Current Pharmaceutical Design Green Synthesis of Metal Nanoparticles from Adiantum Frond: Comparative Analysis on Cancer Cell Lines
Nanoscience & Nanotechnology-Asia