Research team searches for kid-safe drugs
February 14th, 2005
Janice Sullivan (right) and Mary Jayne Kennedy head the U of L Kosair Charities Pediatric Clinical Research Unit. Elizabeth McDowell (front) is a nurse who works in the unit that studies medications in children.
Every day, parents across the United States give their children medication prescribed for everything from the most common of all childhood ailments to rare conditions, and what they might not know could shock them: 75 percent of the medications prescribed in the United States for children have not been studied in children. Of the 80 drugs most frequently given to newborns and infants, only five are labeled for pediatric use.
Janice Sullivan, Mary Jayne Kennedy, collaborating physicians, basic scientists and the other members of the University of Louisville Kosair Charities Pediatric Clinical Research Unit at Kosair Children’s Hospital want to change those statistics. Their unit was established in 2002 to generate scientific data on the effects of medications on children at all stages of development—data that will help pharmaceutical companies provide concrete information about uses of their products in pediatric patients. These findings are expected to lead to more informed prescribing of those medications in children.
“Historically, there have been some significant adverse events with medications in children,” said Sullivan, medical director of the pediatric clinical research unit.
As recently as 10 years ago, the medical community still didn’t realize the dangers of giving medications that have been studied only in adults to children, added Kennedy, a pharmacist and the unit’s associate director.
“It was widely believed that taking an adult dose and scaling it down based on the size of the child was OK,” she said. “But the more we’ve learned about how the body handles and responds to medications during growth and development, we have found better ways to choose the optimal dose for a child. Through scientific advances, we have learned that there are many variables, previously unrecognized by physicians and pharmaceutical companies, that we now must consider.”
“The way the body handles medications is continually changing during the process of growth, making children a moving target from birth to adulthood,” Kennedy said. “At the same time, genetics, environment and disease also affect the way the body handles and responds to a drug. One of our goals is to determine how these variables interact to determine how much medication the child is exposed to following a given dose.”
With this information, “we will ultimately get a better understanding of how to dose the medication in children of different ages,” Sullivan said.
The pediatric clinical research unit has anywhere from 12 to 20 trials in progress at any time. Investigators have studied medications for asthma, botulism, high blood pressure, infections, pain, septic shock, blood-clotting abnormalities and many more conditions.
Significant legislation since 1994 has pretty much forced drug companies into researching medications in children, Sullivan said.
Some of that legislation also led to the formation in 1994 of the Pediatric Pharmacology Research Unit (PPRU) Network, a group formed by the National Institute of Child Health and Human Development (NICHD). It includes 13 American pediatric pharmacology research units, including the one at U of L.
In October 2003 Sullivan and Kennedy learned that they had been awarded a five-year renewable $1.8 million grant to support their participation in the PPRU network. That funding was followed by another $3 million in 2005 federal earmarks secured by U.S. Sen. Mitch McConnell.
Among other things, the funding will support development of the independent Pediatric Clinical Proteomics Center. Proteomics focuses on the products of genes and how changes in specific patterns of proteins affect the body’s functions. The pediatric research unit is working with Jon B. Klein, director of the U of L Core Proteomics Laboratory, to develop the new center.
Many of the PPRU network trials are pharmaceutical company-sponsored studies that provide new information either about how to dose a particular drug for children or about side effects the medicine might cause in children. This information will help the Federal Drug Administration label drugs for use in children.
But even when these data are determined, one question can remain: “Why?”
“If the results of a clinical trial suggest that children respond to or handle a medication differently than adults or children of other ages, it is important to understand the reasons these differences exist,” Kennedy said.
That’s where the Pediatrics Clinical Proteomics Center will play a huge role. Sullivan, Kennedy and their colleagues in the basic and clinical sciences will conduct studies to evaluate the effects of normal growth, development, disease and genetics on proteins that play a role in disease processes and on enzymes and receptors responsible for drug metabolism and action.
Proteomics research has been done in adults for several years, Kennedy said, “but not many investigators have applied this tool in children. We are adapting this technology so that it can be readily applied in pediatric drug development and monitoring.”
Pediatric proteomics research is possible, in part, because of the funding the pediatric clinical research unit has received to support its participation in the PPRU network. The benefits of being in the network, however, extend beyond new labs, equipment and funding, Sullivan said.
Through network membership, pediatric clinical research unit investigators have “an opportunity to interact and collaborate with some of the key pediatric pharmacology units around the nation,” she said.
“As an investigator, if I create a clinical study protocol and need to enroll a large number of subjects, I can take the protocol to the network and have people across the network recruiting patients collaboratively,” Kennedy said. “We can work together to conduct trials that we probably could not have completed alone.”
“Over the next several years, we’ll see more advances in pediatric clinical pharmacology,” Sullivan added. “We still have about 75 percent of medications that are not approved for children. Hopefully, we can make a dent in that over the next 10 years.”
Excerpted from an article by Kevin Hyde in the Winter 2005 issue of U of L magazine.
