Abstract
Background: Differences in drug response among patients are common. Most major drugs are effective in only 25 to 60 percent of the patients, in part due to the CYP enzymes, whose activity vary up to 50-fold between individuals for some index metabolic reactions. Several factors affect CYP activity, among which genetic polymorphisms have been studied as the major cause for long time. Age, gender, disease states, and environmental influences such as smoking, concomitant drug treatment or exposure to environmental chemicals are also important.
Methods: This article reviews the available literature on multiple phenotypes assessment as an important tool to predict possible therapeutic failures or toxic reactions to conventional drug doses during patient evaluation. Results: Probe drugs can be used in various combinations allowing for the in vivo assessment of multiple pathways of drug metabolism in a single experiment, configuring a new tool known as phenotyping "cocktails". There are several drug cocktails with different advantages and disadvantages. Most of them have sufficient clinical evidence and data validation to support their use in clinical setting as a surrogate for the risk of adverse reaction in the course of therapy, leading to a better balance between efficacy and safety. Conclusion: Probes characteristics and metabolic ratio measurements are important in the evaluation of phenotyping cocktails as near-future applications.Keywords: Pharmacogenomics, phenotype, cytochrome P450, genotype, probe, cocktail, polymorphism.
Current Pharmaceutical Design
Title:In vivo Phenotyping Methods: Cytochrome P450 Probes with Emphasis on the Cocktail Approach
Volume: 23 Issue: 14
Author(s): Guillermo Alberto Keller*, María Laura Ferreirós Gago, Roberto Alejandro Diez and Guillermo Di Girolamo
Affiliation:
- Segunda Cátedra de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155 – Piso 16, C1121ABG Ciudad Autónoma de Buenos Aires,Argentina
Keywords: Pharmacogenomics, phenotype, cytochrome P450, genotype, probe, cocktail, polymorphism.
Abstract: Background: Differences in drug response among patients are common. Most major drugs are effective in only 25 to 60 percent of the patients, in part due to the CYP enzymes, whose activity vary up to 50-fold between individuals for some index metabolic reactions. Several factors affect CYP activity, among which genetic polymorphisms have been studied as the major cause for long time. Age, gender, disease states, and environmental influences such as smoking, concomitant drug treatment or exposure to environmental chemicals are also important.
Methods: This article reviews the available literature on multiple phenotypes assessment as an important tool to predict possible therapeutic failures or toxic reactions to conventional drug doses during patient evaluation. Results: Probe drugs can be used in various combinations allowing for the in vivo assessment of multiple pathways of drug metabolism in a single experiment, configuring a new tool known as phenotyping "cocktails". There are several drug cocktails with different advantages and disadvantages. Most of them have sufficient clinical evidence and data validation to support their use in clinical setting as a surrogate for the risk of adverse reaction in the course of therapy, leading to a better balance between efficacy and safety. Conclusion: Probes characteristics and metabolic ratio measurements are important in the evaluation of phenotyping cocktails as near-future applications.Export Options
About this article
Cite this article as:
Keller Alberto Guillermo*, Gago Laura Ferreirós María, Diez Alejandro Roberto and Di Girolamo Guillermo, In vivo Phenotyping Methods: Cytochrome P450 Probes with Emphasis on the Cocktail Approach, Current Pharmaceutical Design 2017; 23 (14) . https://dx.doi.org/10.2174/1381612823666170207100724
DOI https://dx.doi.org/10.2174/1381612823666170207100724 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
Blood-based biomarkers in large-scale screening for neurodegenerative diseases
Disease biomarkers are necessary tools that can be employ in several clinical context of use (COU), ranging from the (early) diagnosis, prognosis, prediction, to monitor of disease state and/or drug efficacy. Regarding neurodegenerative diseases, in particular Alzheimer’s disease (AD), a battery of well-validated biomarkers are available, such as cerebrospinal fluid ...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
Diabetes mellitus: advances in diagnosis and treatment driving by precision medicine
Diabetes mellitus (DM) is a chronic degenerative metabolic disease with ever increasing prevalence worldwide which is now an epidemic disease affecting 500 million people worldwide. Insufficient insulin secretion from pancreatic β cells unable to maintain blood glucose homeostasis is the main feature of this disease. Multifactorial and complex nature of ...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
- 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
-
N-acetylcysteine Exerts Protective Effects and Prevents Lung Redox Imbalance and Peroxynitrite Generation in Endotoxemic Rats
Medicinal Chemistry Diabetic Neuropathy: Update on Pathophysiological Mechanism and the Possible Involvement of Glutamate Pathways
Current Diabetes Reviews Nitrergic Modulation of Gastrointestinal Function During Early Endotoxemia
Current Pharmaceutical Design Non-viral Gene Delivery and Therapeutics Targeting to Brain
Current Nanoscience Clinical Efficacy of Remdesivir and Favipiravir in the Treatment of COVID-19 Patients: Scenario so far
Current Drug Research Reviews Medicinal Chemistry Updates on Bacterial Efflux Pump Modulators
Current Medicinal Chemistry Anticancer Properties of Essential Oils: An Overview
Current Cancer Drug Targets Sudden Infant Death Syndrome: Implications of Altered Physiological Control During Sleep
Current Pediatric Reviews Neurokinin-1 Receptor (NK-1R) Antagonists: Potential Targets in the Treatment of Glioblastoma Multiforme
Current Medicinal Chemistry Chilling-Like Attacks Terminated by Slow Pathway Ablation
Current Cardiology Reviews Amine Oxidase Inhibitors and Development of Neuroprotective Drugs
Current Neuropharmacology Tremor and Rigidity in Patients with Parkinson’s Disease: Emphasis on Epidemiology, Pathophysiology and Contributing Factors
CNS & Neurological Disorders - Drug Targets Biofunctional Peptides from Milk Proteins: Mineral Binding and Cytomodulatory Effects
Current Pharmaceutical Design The Adult Patient with Eisenmenger Syndrome: A Medical Update after Dana Point Part II: Medical Treatment - Study Results
Current Cardiology Reviews Herbal Medicine of the 21st Century: A Focus on the Chemistry, Pharmacokinetics and Toxicity of Five Widely Advocated Phytotherapies
Current Topics in Medicinal Chemistry Proteinase-Activated Receptor-2: Physiological and Pathophysiological Roles
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Design, Synthesis, Pharmacological Evaluation and Descriptor Based Similarities Study of N,N-diphenyl-2-[4-(substituted phenyl)piperazin-1- yl]acetamides as Potential Antipsychotics
Medicinal Chemistry Identification of L-Amino Acid Oxidase (Mb-LAAO) with Antibacterial Activity in the Venom of Montivipera bornmuelleri, a Viper from Lebanon
Infectious Disorders - Drug Targets Reducing Perioperative Myocardial Infarction with Anesthetic Drugs and Techniques
Current Drug Targets Radiolabeled Compounds in Diagnosis of Infectious and Inflammatory Disease
Current Pharmaceutical Design