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Metabolic effects of heterocyclic amines on insulin‑induced AKT phosphorylation and gluconeogenic gene expression are modified by N-acetyltransferase 2 genetic polymorphism.
Pharmacogenet Genomics
January 2025
Department of Pharmacology & Toxicology and Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky, USA.
Objective: Heterocyclic amines (HCAs) are mutagens and carcinogens primarily generated when cooking meat at high temperatures or until well-done, and their major metabolic pathway includes hepatic N-hydroxylation via CYP1A2 followed by O-acetylation via N-acetyltransferase 2 (NAT2). NAT2 expresses a well-defined genetic polymorphism in humans resulting in rapid and slow acetylators. Recent epidemiological studies reported significant associations between dietary HCA exposure and insulin resistance and type II diabetes.
View Article and Find Full Text PDFPharmacokinetic Analysis of an Isoniazid Suspension Among Spanish Children Under 6 Years of Age.
Antibiotics (Basel)
January 2025
Malalties Infeccioses i Resposta Inflamatòria Sistèmica en Pediatria, Servei d'Infectologia, Institut de Recerca Pediàtrica Sant Joan de Déu, 08950 Barcelona, Spain.
: Isoniazid (INH) remains a first-line drug for the treatment of tuberculosis (TB) in young children. In 2010, the WHO recommended an increase in the daily dose of INH up to 10 (7-15) mg/kg. Currently, there are no INH suspensions available in Europe.
View Article and Find Full Text PDFPhenytoin toxicity caused by a drug-to-drug interaction between phenytoin and antitubercular therapy.
BMJ Case Rep
January 2025
Internal Medicine, All India Institute of Medical Sciences - Rishikesh, Rishikesh, Uttarakhand, India.
Phenytoin is one of the most used antiepileptic drugs. Isoniazid, a first-line antitubercular drug, blocks the CYP2C19 enzyme, preventing phenytoin from being metabolised. Concomitant use of phenytoin and isoniazid predisposes to phenytoin toxicity.
View Article and Find Full Text PDFEffect of Genetic Variants on Rosuvastatin Pharmacokinetics in Healthy Volunteers: Involvement of , and .
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 PDFNAT2 Slow Acetylator Phenotype as a Significant Risk Factor for Hepatotoxicity Caused by Antituberculosis Drugs: Results From a Multiethnic Nested Case-Control Study.
Clin 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.
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