Personalized medicine uses technology to enable a level of personalization not previously practical. Currently, tuberculosis (TB) therapy is not personalized. Previous reports have shown that a genetic polymorphism of NAT2 is associated with large interindividual and inter-racial differences in the toxicity and efficacy of isoniazid. Herein, we show the safety and efficacy of a pharmacogenetics-based standard TB therapy and also provide a schematic presentation that proposed therapeutic approaches for latent TB infection (LTBI) using NAT2 genotyping. Our data show that the pharmacogenetics-based TB therapy is safer and more efficacious than the standard therapy. Therefore, the therapy using NAT2 genotyping proposed for LTBI herein will be safer and more efficacious than the standard LTBI therapy. Introduction of this therapy with NAT2 genotyping will be one of the cornerstones of personalized medicine.
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http://dx.doi.org/10.2217/pgs.14.38 | DOI Listing |
Int J Mol Sci
December 2024
Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria La Princesa (IIS-Princesa), 28006 Madrid, Spain.
Statins are the primary drugs used to prevent cardiovascular disease by inhibiting the HMG-CoA reductase, an enzyme crucial for the synthesis of LDL cholesterol in the liver. A significant number of patients experience adverse drug reactions (ADRs), particularly musculoskeletal problems, which can affect adherence to treatment. Recent clinical guidelines, such as those from the Clinical Pharmacogenetics Implementation Consortium (CPIC) in 2022, recommend adjusting rosuvastatin doses based on genetic variations in the and genes to minimize ADRs and improve treatment efficacy.
View Article and Find Full Text PDFBMJ Open
December 2024
Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Central, Uganda.
Introduction: Tuberculosis (TB) is the leading infectious cause of death globally. Despite WHO recommendations for TB preventive therapy (TPT), challenges persist, including incompletion of treatment and adverse drug reactions (ADRs). There is limited data on the 3-month isoniazid and rifapentine (3HP) pharmacokinetics, pharmacogenomics and their relation with ADRs.
View Article and Find Full Text PDFClin Infect Dis
December 2024
III Infectious Disease Unit, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, Milan, Italy.
Background: Under standard therapies, the incidence of drug-induced liver injury (DILI) in patients with tuberculosis ranges from 2% to 28%. Numerous studies have identified the risk factors for antituberculosis DILI; however, none have been conducted in a multiethnic real-world setting. The primary outcome of the current study was to identify the risk factors that could be used as the best predictors of DILI in a multiethnic cohort.
View Article and Find Full Text PDFPharmacol Res Perspect
February 2025
Department of Clinical Pharmacology, Wroclaw Medical University, Wroclaw, Poland.
The enzyme N-acetyltransferase 2 (NAT2) plays an important role in metabolism and detoxification of xenobiotics, including carcinogens and medications. We aimed to assess the contribution of the NAT2 polymorphism to susceptibility to inflammatory bowel disease (IBD) in the Polish population. The study involved 101 IBD patients and 100 healthy controls.
View Article and Find Full Text PDFMonaldi Arch Chest Dis
December 2024
Department of Clinical Pharmacology, Topiwala National Medical College And Bai Yamunabai Laxman Nair Charitable Hospital, Mumbai.
The N-acetyltransferase 2 (NAT2) gene exhibits substantial genetic diversity, leading to distinct acetylator phenotypes among individuals. In this study, we determine NAT2 gene polymorphisms in tuberculosis (TB) patients and analyze serum isoniazid (INH) concentrations across the various genotypes. An observational prospective cohort study involving 217 patients with pulmonary or extrapulmonary TB was carried out.
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