We describe a multi-scale, liver-centric in silico modeling framework for acetaminophen pharmacology and metabolism. We focus on a computational model to characterize whole body uptake and clearance, liver transport and phase I and phase II metabolism. We do this by incorporating sub-models that span three scales; Physiologically Based Pharmacokinetic (PBPK) modeling of acetaminophen uptake and...

Acetaminophen (APAP) is an analgesic and antipyretic agent which may cause hepatotoxicity and nephrotoxicity with overdose in man and laboratory animals. In vivo studies suggest that in situ activation of APAP contributes to the development of nephrotoxicity. Associated with target organ toxicity is selective arylation of proteins, with a 58-kDa acetaminophen binding protein (58-ABP) being the ...

Aim: To study the comparative hepatoprotective effect of Virgin Coconut Oil (VCO) and Neem (Azadirachta indica) leaf extract in acetaminophen (Paracetamol) induced liver toxicity. Methods: About 60 mixed population rats (male/female) Wistar Sprague-Dawley species were randomly selected for proposed are segregated into four equal groups. Every group contains 15 animal subjects. Group A was contr...

Identifying indices of poor prognosis at first presentation after acetaminophen poisoning is the key to both improving clinical care and determining targets for intervention. This study intended to document the prevalence, clinical characteristics and predictors of vomiting and to investigate the relationship between episodes of vomiting at first hospital presentation and outcome in acetaminoph...

"Intrinsic" and "idiosyncratic" drug-induced liver injury reactions are commonly thought to arise by different modes of action. Intrinsic toxicity is reproducible in animals and occurs dose-dependently at sublethal doses. Environmental and genetic sensitivity factors can influence the toxicity of intrinsic hepatotoxicants. Among these is inflammatory stress. For example, exposure of mice to inf...

PURPOSE Toxicity caused by acetaminophen and its toxic mechanisms in the liver have been widely studied, including effects involving metabolism and oxidative stress. However, its adverse effects on heart have not been sufficiently investigated. This study evaluated the cardiac influence and molecular events occurring within the myocardium in rats treated with a dose of acetaminophen large enoug...

BACKGROUND N-acetylcysteine is used to treat acetaminophen toxicity and is available in both intravenous and oral formulations. Our report describes a patient treated with intravenous N-acetylcysteine for acetaminophen toxicity who died after an anaphylactoid reaction following initiation of the infusion. OBJECTIVE Clinicians should be aware of potential complications when deciding on which f...

Background: Acetaminophen (APAP) is a common analgesic and antipyretic medicine that can lead to acute liver injury at high doses. Crocin, Crocus sativus’ ingredient, has potent antioxidant effects. Objectives: This study examined the protective effects of crocin against APAP-induced oxidative stress in mice. Methods: In this study, 56 mice were randomly divided into seven groups (n = 8 per gro...

OBJECTIVE To assess the effect of the UK Committee on Safety of Medicines' announcement in January 2005 of withdrawal of co-proxamol on analgesic prescribing and poisoning mortality. DESIGN Interrupted time series analysis for 1998-2007. SETTING England and Wales. DATA SOURCES Prescribing data from the prescription statistics department of the Information Centre for Health and Social Care...

OBJECTIVES The risk of acute myocardial infarction (AMI) with COX-2 inhibitors may offset their gastrointestinal (GI) benefit compared with non-selective (NS) non-steroidal anti-inflammatory drugs (NSAIDs). We aimed to compare the risks of hospitalization for AMI and GI bleeding among elderly patients using COX-2 inhibitors, NS-NSAIDs and acetaminophen. METHODS We conducted a retrospective co...