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ACHRI Receives $2 Million from NIH to Study Adverse Effects of Common Pain Killer

Publication Date: Tuesday, October 20, 2009

LITTLE ROCK, AR. (Oct. 20, 2009) – Researchers at Arkansas Children’s Hospital Research Institute (ACHRI) recently received a $2 million grant from the National Institutes of Health to determine if some children are at higher risk for toxicity associated with a common over-the-counter pain medicine.

“Acetaminophen is the most widely used drug for treating pain and fever in the world,” said Laura James, MD, the study’s lead investigator and a clinical pharmacologist and toxicologist at Arkansas Children’s Hospital (ACH). Acetaminophen is found in over 100 over-the-counter products. “While we believe it’s safe at recommended doses, we also know that acetaminophen toxicity is one of the major causes of acute liver failure. This research could bring us one step closer to being able to predict which children are likely to have increased susceptibility to liver injury from acetaminophen.”

James also is a professor in the Department of Pediatrics at the University of Arkansas for Medical Sciences (UAMS) and chief of Clinical Pharmacology and Toxicology at ACH.

Although therapeutic doses recommended by the manufacturer are generally considered safe, large doses of acetaminophen can result in severe liver injury, and some individuals may have increased susceptibility. Overdoses of acetaminophen account for a large portion of calls to poison control centers annually, and typically more than 100,000 phone calls related to possible acetaminophen overdose/toxicity occur each year in the United States. This study will address whether there are factors other than the dose of the drug that predispose patients to toxicity.

The five-year study will track patients who have been prescribed therapeutic doses of the over-the-counter drug by physicians as a part of standard inpatient treatment at six hospitals around the United States. Data from these patients will be compared with data from diagnosed cases of acetaminophen toxicity that are seen in emergency rooms at the same sites.

The scientists will study the cases to see if there are similarities in how the acetaminophen alters proteins in the patients’ blood samples. The research could lead to a profile of biomarkers that would designate some children as facing a higher risk for acetaminophen toxicity.

The research is a collaborative effort among investigators at several institutions. They include Dean Roberts, PhD, a research associate professor in the College of Medicine at UAMS, and Dr. Jack Hinson, PhD, a professor and director of the Division of Toxicology in the UAMS College of Medicine.

In addition, investigators from the Proteomics Core Laboratory at the University of Arkansas for Medical Sciences and the Metabolomics Laboratory at the National Center for Toxicological Research will participate in the analysis of samples.

The study will be performed in collaboration with other pediatric researchers who are members of the Pediatric Pharmacology Research Unit (PPRU) Network, which is funded by the National Institute of Child Health and Human Development. Arkansas Children’s Hospital has participated in the PPRU Network since 1994, and Dr. James is principal investigator of the ACHRI PPRU.

“Together, we’ll be looking for any risk factors we can uncover in these kids that may predispose them to adverse health effects from the use of acetaminophen,” James said. “We’re hoping to find diagnostic features that forecast increased susceptibility to acetaminophen toxicity so that we can prevent toxicity in future patients.”

Preliminary studies to support the project were funded in part by the Arkansas Biosciences Institute, the major research component of the Tobacco Settlement Proceeds Act of 2000.

Arkansas Children’s Hospital is the only pediatric medical center in Arkansas and one of the largest in the United States serving children from birth to age 21. The campus spans 28 city blocks and houses 316 beds, a staff of approximately 500 physicians, 80 residents in pediatrics and pediatric specialties and more than 4,000 employees. The private, nonprofit healthcare facility boasts an internationally renowned reputation for medical breakthroughs and intensive treatments, unique surgical procedures and forward-thinking medical research - all dedicated to fulfilling our mission of enhancing, sustaining and restoring children's health and development. ACH recently ranked No. 85 on FORTUNE 100 Best Companies to Work For®. For more information, visit www.archildrens.org.

ACHRI provides a research environment on the ACH campus to meet the needs of the UAMS faculty. Research scientists at ACHRI conduct clinical, basic science, and health services research for the purpose of treating illnesses, preventing disease and improving the health of children everywhere.

UAMS is the state’s only comprehensive academic health center, with five colleges, a graduate school, a new 540,000-square-foot hospital, six centers of excellence and a statewide network of regional centers. UAMS has 2,652 students and 733 medical residents. Its centers of excellence include the Winthrop P. Rockefeller Cancer Institute, the Jackson T. Stephens Spine & Neurosciences Institute, the Myeloma Institute for Research and Therapy, the Harvey & Bernice Jones Eye Institute, the Psychiatric Research Institute and the Donald W. Reynolds Institute on Aging. It is the state’s largest public employer with more than 10,000 employees, including nearly 1,150 physicians who provide medical care to patients at UAMS, Arkansas Children’s Hospital, the VA Medical Center and UAMS’ Area Health Education Centers throughout the state. Visit www.uams.eduor www.uamshealth.com.

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