Despite the widespread use of cyclophosphamide to treat a wide variety of cancers, relatively little is known about how it is metabolized in infants and children. Some of the complicated metabolic reactions of this drug cause tumor cells to die while others cause severe side effects. Because the relationship between development, genetic make-up and drug exposure remains largely unexplored, pediatricians may not be giving the best possible dose to their patients.

     Understanding how cyclophosphamide is metabolized in children is the focus of a study directed by Andrea Gaedigk, MS, PhD, Clinical Pharmacology and Jignesh Dalal, MD, Bone Marrow Transplantation, experts in the fields of pharmacogenetics and pediatric oncology. It is supported by the Tom Keaveny Endowed Fund for Pediatric Cancer Research.

     "The amount of enzymes that metabolize certain drugs varies considerably from person to person, which is mostly due to a person's genetic make-up," says Dr. Gaedigk. "An additional layer of complexity is that many of these drug-metabolizing enzymes ‘turn on' at variable times after birth, usually during the first year of life. Choosing the right drug and the right dose in order to maximize benefits while limiting adverse effects remains a huge challenge, especially in our youngest patients."

     According to Dr. Gaedigk, there is still a big knowledge deficit about how drugs work in very, very young children that drives her inquiry into the variability of these enzymes.

     "Children are not just little adults," says Dr. Gaedigk. "This research will help give us a better understanding of how this drug should be dosed for children. Since it can make them very sick, every bit that we can reduce the amount they get and still receive the benefits will help."

     Getting in on the ground floor of a revolutionary new field opened up a fascinating career path for Andrea Gaedigk, MS, PhD. While pursuing her doctorate in her native Germany, she had the opportunity to work with Michel Eichelbaum, MD, one of the early pioneers of pharmacogenetics.

     "It was an emerging field at that time and very exciting," says Dr. Gaedigk. "I had a chance to get in and I jumped on it."

     Dr Gaedigk's major research interest is how genetic factors affect drug metabolism. She is involved in a number of studies spanning a variety of drugs, including codeine (pain medication), dextromethorphan (a component of cold medication) and warfarin (an anticoagulant).

     Looking ahead, the promise that pharmacogenetics holds for the future seems even greater now than when she first entered the field.

     "The ultimate goal is to get the right drug to the right person at the right dose," says Dr. Gaedigk, who chairs the Basic Science Research Committee. "We're generating tremendous amounts of data to help us know how to do that. The challenge is understanding what it all means."