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The role of corticosterone in nevirapine-induced idiosyncratic drug-induced liver injury.
Toxicol Sci
June 2024
Department of Pharmacology & Toxicology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 3M2, Canada.
Nevirapine, an antiretroviral used in the treatment of HIV, is associated with idiosyncratic drug-induced liver injury (IDILI), a potentially life-threatening adverse drug reaction. Its usage has decreased due to this concern, but it is still widely used in lower-resource settings. In general, the mechanisms underlying idiosyncratic drug reactions (IDRs) are poorly understood, but evidence indicates that most are immune-mediated.
View Article and Find Full Text PDFNevirapine-induced Stevens-Johnson syndrome in children living with HIV in South Africa.
South Afr J HIV Med
February 2021
HIV Outpatient Department, Zithulele Hospital, Mqanduli, South Africa.
Background: Although adverse drug reactions resulting from the use of nevirapine (NVP) are well described in adults (estimated frequency of 6% - 10%), it has previously been considered less common in children (0.3% - 1.4%).
View Article and Find Full Text PDFInvestigating the Mechanism of Trimethoprim-Induced Skin Rash and Liver Injury.
Toxicol Sci
February 2021
Leslie Dan Faculty of Pharmacy, Faculty of Medicine, University of Toronto, Toronto M5S3M2, Canada.
Trimethoprim (TMP)-induced skin rash and liver injury are likely to involve the formation of reactive metabolites. Analogous to nevirapine-induced skin rash, 1 possible reactive metabolite is the sulfate conjugate of α-hydroxyTMP, a metabolite of TMP. We synthesized this sulfate and found that it reacts with proteins in vitro.
View Article and Find Full Text PDFAnti-HIV drugs promote β-amyloid deposition and impair learning and memory in BALB/c mice.
Acta Neuropsychiatr
October 2020
School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Objectives: Growing evidence suggested that antiretroviral (ARV) drugs may promote amyloid beta (Aβ) accumulation in HIV-1-infected brain and the persistence of HIV-associated neurocognitive disorders (HANDs). It has also been shown that lipid peroxidation upregulates β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) expression and subsequently promotes Aβ peptide production. In the present study, we examined whether chronic exposure to the anti-HIV drugs tenofovir disoproxil fumarate (TDF) and nevirapine induces lipid peroxidation thereby promoting BACE1 and Aβ generation and consequently impair cognitive function in mice.
View Article and Find Full Text PDFTwelfth-Position Deuteration of Nevirapine Reduces 12-Hydroxy-Nevirapine Formation and Nevirapine-Induced Hepatocyte Death.
J Med Chem
June 2020
Department of Pharmacology & Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States.
Cytochrome P450-dependent metabolism of the anti-HIV drug nevirapine (NVP) to 12-hydroxy-NVP (12-OHNVP) has been implicated in NVP toxicities. We investigated the impact of twelfth-position trideuteration (12-DNVP) on the hepatic metabolism of and response to NVP. Formation of 12-OHNVP decreased in human (10.
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