Abstract
The evolution of research on drug protein binding is discussed with the unbound concentration (Cu) and the unbound fraction (fu) as protagonists. Particular attention is paid to the mechanisms via which alterations in binding affect the pharmacokinetics (PK) and the effect, or independently the pharmacodynamics (PD). Apart from albumin, the important α-acid glycoprotein (AGP), as well as specific drug classes and applications in the clinic and development (routine monitoring, cancer and HIV therapy, allometry) are addressed. The flaws with the classical method of indirectly calculating the Cu or the unbound PK/PD parameters, based on the fu in vitro, are related to the intrinsic complexity and variability in the outcomes. Increased focus is urged on directly estimating the unbound PK/PD and also on using population statistical methods.
Keywords: Unbound drug, protein binding, AGP variability, PK/PD
Current Pharmaceutical Design
Title: The Role of Unbound Drug in Pharmacokinetics/Pharmacodynamics and in Therapy
Volume: 12 Issue: 8
Author(s): Rosario Calvo, John C. Lukas, Monica Rodriguez, Nerea Leal and Elena Suarez
Affiliation:
Keywords: Unbound drug, protein binding, AGP variability, PK/PD
Abstract: The evolution of research on drug protein binding is discussed with the unbound concentration (Cu) and the unbound fraction (fu) as protagonists. Particular attention is paid to the mechanisms via which alterations in binding affect the pharmacokinetics (PK) and the effect, or independently the pharmacodynamics (PD). Apart from albumin, the important α-acid glycoprotein (AGP), as well as specific drug classes and applications in the clinic and development (routine monitoring, cancer and HIV therapy, allometry) are addressed. The flaws with the classical method of indirectly calculating the Cu or the unbound PK/PD parameters, based on the fu in vitro, are related to the intrinsic complexity and variability in the outcomes. Increased focus is urged on directly estimating the unbound PK/PD and also on using population statistical methods.
Export Options
About this article
Cite this article as:
Calvo Rosario, Lukas C. John, Rodriguez Monica, Leal Nerea and Suarez Elena, The Role of Unbound Drug in Pharmacokinetics/Pharmacodynamics and in Therapy, Current Pharmaceutical Design 2006; 12 (8) . https://dx.doi.org/10.2174/138161206776055967
DOI https://dx.doi.org/10.2174/138161206776055967 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
A Fresh Prospect of Extracellular Matrix Hydrolytic Enzymes and Their Substrates
Current Pharmaceutical Design Immunotherapy of Acute Myeloid Leukemia
Current Pharmaceutical Biotechnology Neurodegenerative Disease: A Perspective on Cell-Based Therapy in the New Era of Cell-Free Nano-Therapy
Current Pharmaceutical Design Long Noncoding RNA C21orF96 Promotes the Migration, Invasion and Lymph Node Metastasis in Gastric Cancer
Anti-Cancer Agents in Medicinal Chemistry Synthetic Approach for Substituted 3-Amino-1,2,4-Triazines and their Chemical Reactivity and Biological Properties
Mini-Reviews in Organic Chemistry Implications of FLT3 Mutations in the Therapy of Acute Myeloid Leukemia
Reviews on Recent Clinical Trials Computational Methods and Algorithms for Mass Spectrometry Based Differential Proteomics: Recent Advances, Perspectives and Open Problems
Current Proteomics MicroRNAs: Key Players in Microglia and Astrocyte Mediated Inflammation in CNS Pathologies
Current Medicinal Chemistry Interaction of Biologically Active Amines with Mitochondria and Their Role in the Mitochondrial-Mediated Pathway of Apoptosis
Current Medicinal Chemistry Dry Powder Formulation of Plasmid DNA and siRNA for Inhalation
Current Pharmaceutical Design Radiosensitizing Potential of Epigenetic Anticancer Drugs
Anti-Cancer Agents in Medicinal Chemistry Recent Advances in Peptide-Based Approaches for Cancer Treatment
Current Medicinal Chemistry Chemoinformatic Analysis of Biologically Active Macrocycles
Current Topics in Medicinal Chemistry Deciphering the Role of Forkhead Transcription Factors in Cancer Therapy
Current Drug Targets A Review on Structures and Functions of Bcl-2 Family Proteins from Homo sapiens
Protein & Peptide Letters NBN Polymorphysms and Cancer Susceptibility: A Systematic Review
Current Genomics Morphological and Functional Characteristic of Senescent Cancer Cells
Current Drug Targets Pathobiology and Therapeutic Implications of Tumor Acidosis
Current Medicinal Chemistry The Last Decade of Carbon Paste Electrodes in DNA Electrochemistry
Current Analytical Chemistry FtsZ: A Novel Target for Tuberculosis Drug Discovery
Current Topics in Medicinal Chemistry