Tuberculosis is a global pandemic that threatens to overwhelm healthcare budgets in many developing countries. Despite the availability of adequate effective treatment, many patients default on treatment, experience adverse side effects from antibiotics or fail to respond rapidly and recover. Isoniazid, one of the most important first-line tuberculosis drugs, is acetylated in the liver to a variable degree in different individuals giving rise to fast, intermediate and slow acetylator phenotypes. We present the view that the acetylation status of individuals plays an important contributory role in the tuberculosis pandemic. It is important to study the acetylation alleles, and to understand isoniazid metabolism and the manner in which it could affect patient compliance, isoniazid-toxicity and the emergence of drug-resistant strains of mycobacteria.
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http://dx.doi.org/10.2217/17410541.4.2.123 | DOI Listing |
BMJ 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 PDFSci Rep
December 2024
National Biobank of Thailand, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand.
Inter-individual variability in drug responses is significantly influenced by genetic factors, underscoring the importance of population-specific pharmacogenomic studies to optimize clinical outcomes. In this study, we analyzed whole genome sequencing data from 949 unrelated Thai individuals and conducted an in-depth analysis of 3239 genes involved in drug pharmacokinetics, pharmacodynamics, or immune-mediated adverse drug reactions. We identified 43 single nucleotide polymorphisms (SNPs), 134 diplotypes, and 15 human leukocyte antigen (HLA) alleles, all with moderate to high clinical significance.
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.
View Article and Find Full Text PDFFront Pharmacol
November 2024
Department of Pharmacology and Toxicology and Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, United States.
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