Student’s Drug Model Could Mean Better Outcomes for Hepatitis C Patients

Post-doctoral fellow Jin won national award for her “translational” research on mathematical drug dosing model.

By Steve Berberich
December 7, 2010

University of Maryland School of Pharmacy researchers have developed a mathematical model for choosing an appropriate dosage of hepatitis medications for individual patients. The work helps explain why African American patients tend to not respond as well to the drugs as other patients.

For the work, researcher Runyan Jin, MD, PhD, won the best student research award and a $1,000 prize at the 2010 American College of Clinical Pharmacology scientific meeting. Her project involved analyzing 900 blood samples from 400 patients enrolled in a multi-center trial to determine why hepatitis therapy works for some patients but not others.

Hepatitis C is a serious liver disease caused by the hepatitis C virus, and if untreated, can lead to liver cancer and death. African Americans have a higher incidence of the disease and death from liver cancer.

The therapy, consisting of the anti-virus drug ribavirin, along with injections of the protective protein interferon, cures hepatitis C in some patients within six months due to a sustained viral response [SVR], suppressing the virus to undetectable levels for an extended period of time.

“Our question was why some patients in the large trial did not get this SVR cure. The response rate of African American patients was about half that of non-African Americans,” says Thomas Dowling, PharmD, PhD, associate professor of pharmacy practice and science at the School and co-director of its Clinical Pharmacology Unit.

Jin, who is Dowling’s post-doctoral fellow and is already a pediatrician, reported that blood from the African American patients contained lower levels of the ribavirin drug than blood from non-African American patients on the same therapy. Especially in early stages of the therapy, the ribavirin was not getting into the blood system as efficiently in African Americans as in Caucasians. The mathematical model showed that the African Americans had a pharmacodynamic difference somehow in the distributional volume, which means the space where the drug moves, says Dowling.

The different response by African Americans to ribavirin is not the first time medical science has seen such a drug response difference between races.

“We are trying to model how to change the dosage, not just change dose recommendations at this time. Eventually, such personalized therapy will mean proper doses for each patient’s genotype,” says Dowling.

Pediatrician Jin hopes that her research on anti-virus mediations and how they work in different people, an area called pharmacodynamics, will also be useful in treating children. “It is especially important for children to get the correct dosages for safe and effective treatments.”

“I was very lucky,” says Jin. “When I was a second year PhD student, I was looking for a research project in pharmacodynamics.” She applied a mathematical method called Bayesian statistics to simplify the pharmacodynamic relationship between the drug and the 400 patients in the 2006 study, a method taught to her by Michael Fossler, PharmD, PhD, an alum of the School of Pharmacy now with drug maker GlaxoSmithKline.

“Runyan pulled a very nice story together with direct clinical applications. What we are faced with now [in drug development] is studies that are so very expensive, says Fossler. “Bayesian methodology helps us cut our losses and saves some patients from taking drugs that don’t work sometimes.”

Jin’s research poster, “Population Pharmacodynamic Model in Patients with Chronic Hepatitis C Virus Genotype 1,” won the 2010 Wayne A. Colburn Memorial Award at the annual meeting of the American College of Clinical Pharmacology. She has accepted a position at the U.S. Food and Drug Administration In her new career, she says, “I want to be an expert in this area of quantitative clinical pharmacology.”