Abstract
Acetaminophen (APAP) is widely used as an over-the-counter fever reducer and pain reliever. However, the current therapeutic use of APAP is not optimal. The inter-patient variability in both efficacy and toxicity limits the use of this drug. This is particularly an issue in pediatric populations, where tools for predicting drug efficacy and developmental toxicity are not well established. Variability in toxicity between age groups may be accounted for by differences in metabolism, transport, and the genetics behind those differences. While pharmacogenomics has been revolutionizing the paradigm of pharmacotherapy for many drugs, its application in pediatric populations faces significant challenges given the dynamic ontogenic changes in cellular and systems physiology. In this review we focused on the ontogenesis of the regulatory pathways involved in the disposition of APAP and on the variability between pediatric, adolescent, and adult patients. We also summarize important polymorphisms of the pharmacogenes associated with APAP metabolism. Pharmacogenetic studies in pediatric APAP treatment are also reviewed. We conclude that while a consensus in pharmacogenetic management of APAP in pediatric populations has not been achieved, a systems biology based strategy for comprehensively understanding the ontogenic regulatory pathway as well as the interaction between age and genetic variations are particularly necessary in order to address this question.
Highlights
It has been over half a century since acetaminophen (APAP), or paracetamol, was approved by the United States Food and Drug Administration (FDA) to be used as an analgesic and antipyretic
It was found that inhibition of both CYP2E1 and CYP2A6 significantly decreased the formation of N -acetyl-p-benzoquinone imine (NAPQI) (Gonzalez, 2005), suggesting multiple cytochrome P450 (CYP) are involved in the development of APAP hepatotoxicity
Significant inter-patient differences in both APAP PK and toxicity profiles have been observed between adults and children as well as between pediatric populations
Summary
It has been over half a century since acetaminophen (APAP), or paracetamol, was approved by the United States Food and Drug Administration (FDA) to be used as an analgesic and antipyretic. We review the major clinical outcome variability for APAP observed between pediatric and adult patients, as well as among children of different ages. It has been noted that younger children may be less susceptible to APAP-induced hepatotoxicity because of increased glutathione stores or metabolism differences as a result of genetic variability (Pineiro-Carrerro and Pineiro, 2004).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
