Abstract
Tuberculosis (TB) is the leading cause of mortality due to a single infectious agent. The currently used combination drug regimens produce cure rates that exceed 95%, given good patient adherence during the multiple months treatment period. However the recent surge in HIV infections and the synergy between HIV and TB as well as the emergence of resistance resulted in an unforeseen increase in the number of TB cases, including multi-drug resistant (MDR) and extensively-drug resistant (XDR) forms of TB. Consequently, there is an urgent need to develop novel, fast acting antituberculosis drugs with high potency that can provide treatment options for all forms of TB. It is well known that the current TB drugs exhibit differences in their in vivo activity profile and these differences are largely determined by their pharmacodynamics (PD), i.e. intrinsic antibacterial activity, biopharmaceutical properties such as solubility and permeability, and pharmacokinetic (PK) properties such as drug exposure, tissue distribution, and protein binding. An understanding of the relationships among these properties is considered key for a rational use of antituberculosis therapeutics. The current review provides a comprehensive summary of physicochemical/biopharmaceutical, PK, and PD properties of currently used antituberculosis drugs and novel agents under development. Also, a brief review of PK/PD parameters of current TB drugs is given and properties of a desirable TB drug target and drug molecule are outlined. The information provided herewith may be useful in the optimization of biopharmaceutical and PK/PD characteristics in the development of novel TB therapeutics and in the design of optimal treatment regimens.
Keywords: Tuberculosis, antituberculosis drug, pharmacokinetics, pharmacodynamics, biopharmaceutics, drugs development
Current Medicinal Chemistry
Title: Biopharmaceutics, Pharmacokinetics and Pharmacodynamics of Antituberculosis Drugs
Volume: 15 Issue: 8
Author(s): Nageshwar R. Budha, Richard E. Lee and Bernd Meibohm
Affiliation:
Keywords: Tuberculosis, antituberculosis drug, pharmacokinetics, pharmacodynamics, biopharmaceutics, drugs development
Abstract: Tuberculosis (TB) is the leading cause of mortality due to a single infectious agent. The currently used combination drug regimens produce cure rates that exceed 95%, given good patient adherence during the multiple months treatment period. However the recent surge in HIV infections and the synergy between HIV and TB as well as the emergence of resistance resulted in an unforeseen increase in the number of TB cases, including multi-drug resistant (MDR) and extensively-drug resistant (XDR) forms of TB. Consequently, there is an urgent need to develop novel, fast acting antituberculosis drugs with high potency that can provide treatment options for all forms of TB. It is well known that the current TB drugs exhibit differences in their in vivo activity profile and these differences are largely determined by their pharmacodynamics (PD), i.e. intrinsic antibacterial activity, biopharmaceutical properties such as solubility and permeability, and pharmacokinetic (PK) properties such as drug exposure, tissue distribution, and protein binding. An understanding of the relationships among these properties is considered key for a rational use of antituberculosis therapeutics. The current review provides a comprehensive summary of physicochemical/biopharmaceutical, PK, and PD properties of currently used antituberculosis drugs and novel agents under development. Also, a brief review of PK/PD parameters of current TB drugs is given and properties of a desirable TB drug target and drug molecule are outlined. The information provided herewith may be useful in the optimization of biopharmaceutical and PK/PD characteristics in the development of novel TB therapeutics and in the design of optimal treatment regimens.
Export Options
About this article
Cite this article as:
Budha R. Nageshwar, Lee E. Richard and Meibohm Bernd, Biopharmaceutics, Pharmacokinetics and Pharmacodynamics of Antituberculosis Drugs, Current Medicinal Chemistry 2008; 15 (8) . https://dx.doi.org/10.2174/092986708783955509
DOI https://dx.doi.org/10.2174/092986708783955509 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Is Anticoagulation with Novel Oral Anticoagulants an Effective Treatment for Tuberculosis Patients not Achieving a Therapeutic Range with Vitamin K Antagonists? A Systematic Review
Cardiovascular & Hematological Disorders-Drug Targets An Interventional Pulmonologist’s Tool: Endobronchial Ultrasound- Guided Transbronchial Needle Aspiration (EBUS-TBNA) in Thoracic Disease — An Update
Current Respiratory Medicine Reviews Effect of Environmental Substances on the Activity of Arylamine N-Acetyltransferases
Current Drug Metabolism Whole Cell Biocatalysts for the Preparation of Nucleosides and their Derivatives
Current Pharmaceutical Design Clinical and Forensic Aspects of Pharmacobezoars
Current Drug Research Reviews Inhibitors of Glutamine Synthetase and their Potential Application in Medicine
Mini-Reviews in Medicinal Chemistry Microbial Efflux Pump Inhibition: Tactics and Strategies
Current Pharmaceutical Design TNF-Alpha Antagonism in Severe Asthma?
Recent Patents on Inflammation & Allergy Drug Discovery New Insights into Invasive Aspergillosis - from the Pathogen to the Disease
Current Pharmaceutical Design Affordable Antiretroviral Drugs for the Under-Served Markets: How to Expand Equitable Access Against the Backdrop of Challenging Scenarios?
Current HIV Research The Role of Autophagy in Rheumatic Disease
Current Drug Targets Why is the Incidence of Type 1 Diabetes Increasing?
Current Diabetes Reviews Macrophage Targeted Cellular Carriers for Effective Delivery of Anti-Tubercular Drugs
Recent Patents on Anti-Infective Drug Discovery Patent Selections
Recent Patents on Anti-Infective Drug Discovery Synthesis and Molecular Modeling Studies of Novel 2,4-Disubstituted-1, 5-Diphenyl-1-H-Imidazole Derivatives as Potential Anti-Tubercular Agents
Current Bioactive Compounds Anticancer Activities of New N-hetaryl-2-cyanoacetamide Derivatives Incorporating 4,5,6,7-Tetrahydrobenzo[b]thiophene Moiety
Anti-Cancer Agents in Medicinal Chemistry Syntheses of Ethyl Pyruvate’s Bioisosteres Inhibiting Inducible Nitric Oxide Production in Lipopolysaccharide-induced BV2 Cells
Letters in Drug Design & Discovery Trypanosomatid Enzymes as Targets for Plant-Derived Compounds: New Perspectives for Phytotherapeutic Approaches
Current Enzyme Inhibition Immune Mechanisms of Sublingual Immunotherapy and Mycobacterial Adjuvants in the Treatment of Allergic Disease
Current Immunology Reviews (Discontinued) Pathogenesis in Childhood Idiopathic Nephrotic Syndrome: An Update of Patchwork
Current Pediatric Reviews