The current use and future perspectives of molecular genetic characterisation of cytochrome P450 enzymes (CYP) for drug development and drug treatment are summarised. CYP genes are highly polymorphic and the enzymes play a key role in the elimination of the majority of drugs from the human body. Frequent variants of some enzymes, CYP2A6, 2C9, 2C19 and 2D6, should be analysed in participants of clinical trials whenever these enzymes may play a role. It is suggested that a CYP genotype certificate is handed out to the volunteers or patients to avoid replicate analyses, and to allow that this information is available for future research and also for treatment with eventually needed drugs. Guidelines on what CYP alleles have to be analysed in drug development, as well as on analytical validation and CYP genotype data handling will be required. Treatment with several drugs may be improved by prior genotyping. The concepts and problems of CYP genotype-based clinical dose recommendations are presented and illustrated for selected drugs. The requirement for prospective trials on the medical and economic benefits of routine CYP genotyping is emphasised. Specific operationally defined recommendations dependent on genotype are a prerequisite for such studies and this review presents tentative CYP genotype-based dose recommendations systematically calculated from published data. Because of the multiplicity of factors involved, these doses will not be the optimal doses for each given individual, but should be more adequate than doses generally recommended for an average total population. Those CYP alleles and polymorphically metabolised drugs which are currently most interesting in drug development and drug treatment are reviewed, and more complete information is available from websites cited in this article.
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http://dx.doi.org/10.1517/14622416.1.2.125 | DOI Listing |
Front Med (Lausanne)
January 2025
School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom.
Introduction: When implemented by national and regional regulatory agencies good review practices (GRevPs) support the timely high-quality review of medicines for enhanced patients' availability to safe, quality and efficacious innovative and generic products. It is important that all aspects of GRevPs are continuously evaluated and updated to promote the continuous improvement of regulatory systems at national and regional levels. The aim of this study was to assess and compare the GRevPs of the national medicines regulatory agencies (NMRAs) of Burkina Faso, Cote d'Ivoire, Ghana, Nigeria, Senegal, Sierra Leone and Togo, who are active participants of the ECOWASMRH initiative to identify opportunities for improvement.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.
Background: Bladder cancer (BCa) is one of the most common malignancies worldwide, and its prognostication and treatment remains challenging. The fast growth of various cancer cells requires reprogramming of its energy metabolism using aerobic glycolysis as a major energy source. However, the prognostic and therapeutic value of glycolysis-related genes in BCa remains to be determined.
View Article and Find Full Text PDFDrug Des Devel Ther
January 2025
Department of Hematology, Jining NO. 1 People's Hospital, Jining, 272000, People's Republic of China.
Purpose: Mitoxantrone (MTX) is largely restricted in clinical usage due to its significant cardiotoxicity. Multiple studies have shown that an imbalance in the gut-heart axis plays an important role in the development of cardiovascular disease (CVD). We aim to explore the possible correlations between gut microbiota (GM) compositions and cardiometabolic (CM) disorder in MTX-triggered cardiotoxicity mice.
View Article and Find Full Text PDFCytotechnology
April 2025
University Centre for Research and Development, University Institute of Pharmaceutical Sciences, Chandigarh University, Gharuan, Mohali, 140413 India.
When juxtaposed with 2D cell culture models, multicellular tumor spheroids demonstrate a capacity to faithfully replicate certain features inherent to solid tumors. These include spatial architecture, physiological responses, the release of soluble mediators, patterns of gene expression, and mechanisms of drug resistance. The morphological and behavioural similarities between 3D-cultured cells and cells within tumor masses highlight the potential of these models in studying cancer biology and drug responses.
View Article and Find Full Text PDFBreast Cancer (Dove Med Press)
January 2025
Immunology Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, 21859, Saudi Arabia.
Nanoparticle technology has revolutionized breast cancer treatment by offering innovative solutions addressing the gaps in traditional treatment methods. This paper aimed to comprehensively explore the historical journey and advancements of nanoparticles in breast cancer treatment, highlighting their transformative impact on modern medicine. The discussion traces the evolution of nanoparticle-based therapies from their early conceptualization to their current applications and future potential.
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