Systems Toxicology Approach to Identifying Paracetamol Overdose



Mason, Chantelle L, Leedale, Joseph ORCID: 0000-0001-9010-4126, Tasoulis, Sotiris, Jarman, Ian, Antoine, Daniel J and Webb, Steven D
(2018) Systems Toxicology Approach to Identifying Paracetamol Overdose. CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY, 7 (6). pp. 394-403.

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Abstract

Paracetamol (acetaminophen (APAP)) is one of the most commonly used analgesics in the United Kingdom and the United States. However, exceeding the maximum recommended dose can cause serious liver injury and even death. Promising APAP toxicity biomarkers are thought to add value to those used currently and clarification of the functional relationships between these biomarkers and liver injury would aid clinical implementation of an improved APAP toxicity identification framework. The framework currently used to define an APAP overdose is highly dependent upon time since ingestion and initial dose; information that is often highly unpredictable. A pharmacokinetic/pharmacodynamic (PK/PD) APAP model has been built in order to understand the relationships between a panel of biomarkers and APAP dose. Visualization and statistical tools have been used to predict initial APAP dose and time since administration. Additionally, logistic regression analysis has been applied to histology data to provide a prediction of the probability of liver injury.

Item Type: Article
Uncontrolled Keywords: Animals, Humans, Mice, Disease Models, Animal, Acetaminophen, Models, Statistical, Logistic Models, Models, Theoretical, Male, Drug Overdose, Biomarkers, Chemical and Drug Induced Liver Injury
Depositing User: Symplectic Admin
Date Deposited: 20 Apr 2018 15:07
Last Modified: 19 Jan 2023 06:35
DOI: 10.1002/psp4.12298
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3020418