Abstract
The advent of more efficient methods to synthesize and screen new chemical compounds is increasing the number of chemical leads identified in the drug discovery phase. Compounds with good biological activity may fail to become drugs due to insufficient oral absorption. Selection of drug development candidates with adequate absorption characteristics should increase the probability of success in the development phase. To assess the absorption potential of new chemical entities numerous in vitro and in vivo model systems have been used. Many laboratories rely on cell culture models of intestinal permeability such as, Caco-2, HT-29 and MDCK. To attempt to increase the throughput of permeability measurements, several physicochemical methods such as, immobilized artificial membrane (IAM) columns and parallel artificial membrane permeation assay (PAMPA) have been used. More recently, much attention has been given to the development of computational methods to predict drug absorption. However, it is clear that no single method will sufficient for studying drug absorption, but most likely a combination of systems will be needed. Higher throughput, less reliable methods could be used to discover ‘loser’ compounds, whereas lower throughput, more accurate methods could be used to optimize the absorption properties of lead compounds. Finally, accurate methods are needed to understand absorption mechanisms (efflux -limited absorption, carrier-mediated, intestinal metabolism) that may limit intestinal drug absorption. This information could be extremely valuable to medicinal chemists in the selection of favorable chemo-types. This review describes different techniques used for evaluating drug absorption and indicates their advantages and disadvantages.
Current Topics in Medicinal Chemistry
Title: Assessing the Absorption of New Pharmaceuticals
Volume: 1 Issue: 5
Author(s): Ismael J. Hidalgo
Affiliation:
Abstract: The advent of more efficient methods to synthesize and screen new chemical compounds is increasing the number of chemical leads identified in the drug discovery phase. Compounds with good biological activity may fail to become drugs due to insufficient oral absorption. Selection of drug development candidates with adequate absorption characteristics should increase the probability of success in the development phase. To assess the absorption potential of new chemical entities numerous in vitro and in vivo model systems have been used. Many laboratories rely on cell culture models of intestinal permeability such as, Caco-2, HT-29 and MDCK. To attempt to increase the throughput of permeability measurements, several physicochemical methods such as, immobilized artificial membrane (IAM) columns and parallel artificial membrane permeation assay (PAMPA) have been used. More recently, much attention has been given to the development of computational methods to predict drug absorption. However, it is clear that no single method will sufficient for studying drug absorption, but most likely a combination of systems will be needed. Higher throughput, less reliable methods could be used to discover ‘loser’ compounds, whereas lower throughput, more accurate methods could be used to optimize the absorption properties of lead compounds. Finally, accurate methods are needed to understand absorption mechanisms (efflux -limited absorption, carrier-mediated, intestinal metabolism) that may limit intestinal drug absorption. This information could be extremely valuable to medicinal chemists in the selection of favorable chemo-types. This review describes different techniques used for evaluating drug absorption and indicates their advantages and disadvantages.
Export Options
About this article
Cite this article as:
Ismael J. Hidalgo , Assessing the Absorption of New Pharmaceuticals, Current Topics in Medicinal Chemistry 2001; 1 (5) . https://dx.doi.org/10.2174/1568026013395010
DOI https://dx.doi.org/10.2174/1568026013395010 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
- Announcements
Related Articles
-
Impact of Mitochondrial Toxicity of HIV-1 Antiretroviral Drugs on Lipodystrophy and Metabolic Dysregulation
Current Pharmaceutical Design Small Molecular Weight Inhibitors of Stress-Activated and Mitogen- Activated Protein Kinases
Mini-Reviews in Medicinal Chemistry Challenging Treatment-Resistant Major Depressive Disorder: A Roadmap for Improved Therapeutics
Current Neuropharmacology Iontophoresis: Drug Delivery System by Applying an Electrical Potential Across the Skin
Drug Delivery Letters The Expanding Role of TNF-Receptor Super Family Member CD40 (tnfrsf5) in Autoimmune Disease: Focus on Th40 Cells
Current Immunology Reviews (Discontinued) Bile Salt Stabilized Vesicles (Bilosomes): A Novel Nano-Pharmaceutical Design for Oral Delivery of Proteins and Peptides
Current Pharmaceutical Design Bioactivities of Rubidium Chloride-Poly (4-Vinylpyridine) Composite Fabricated Via Sol Gel Technique
Current Pharmaceutical Analysis The Role of Biotransformation in the Activity of Endocrine Disruptors
Current Drug Metabolism N-Heterocyclic Dronic Acids: Applications and Synthesis
Mini-Reviews in Medicinal Chemistry Editorial [Hot Topic: Telomeres and Telomerase in Diseases, Aging, and Carcinogenesis (Executive Editor: K. Lenhard Rudolph)]
Current Molecular Medicine Inhibitory Effect of Ebselen on Cerebral Acetylcholinesterase Activity In Vitro: Kinetics and Reversibility of Inhibition
Current Pharmaceutical Design Clinical Approaches Toward Tumor Angiogenesis: Past, Present and Future
Current Pharmaceutical Design Adverse Reactions and Pathogen Safety of Intravenous Immunoglobulin
Current Drug Safety Caffeic Acid Phenethyl Ester: A Potential Anticancer Bioactive Constituent of Propolis
Current Cancer Therapy Reviews A Retrospective Study on Advanced Maternal Age and Assisted Reproductive Techniques, Medico-Legal Advice, “Food for Thought”
Current Pharmaceutical Biotechnology Multi-Functional Anti-HIV Agents Based on Amino Acid Sequences Present in Serpin C-Terminal Peptides
Anti-Infective Agents in Medicinal Chemistry A Study of Prescription Pattern and Compliance of Anti-hypertensives with the Treatment Guidelines in Aseer Region; Saudi Arabia
Current Drug Therapy Galectin-1 is a Novel Factor that Regulates Myotube Growth in Regenerating Skeletal Muscles
Current Drug Targets Dexmedetomidine: A Novel Anesthetic Agent for Middle Ear Surgery
Recent Patents on CNS Drug Discovery (Discontinued) Blood Pressure and White Matter Lesions in Patients with Vascular Disease: The SMART-MR Study
Current Neurovascular Research