Developing Computer Models for Personalized Drug Dosing
"Developing better methods for individual drug dosing" is how Alexander (Sander) Vinks, PharmD, PhD, describes the motivating force behind his current clinical pharmacology research projects. As director of the Pediatric Pharmacology Research Unit and Laboratory of Applied Pharmacokinetics and Therapeutic Drug Management at Cincinnati Children's, Dr. Vinks is principal investigator for several studies examining variations in how pediatric patients absorb and metabolize drugs and what role genetics may play in these variations and therapeutic responses.
"Imagine if we could accurately predict drug exposure and response before the first dose even was given," Dr. Vinks says. "Armed with the right tools, we could predict the likelihood that the drug and the dosing regimen selected would give the best possible response with the least chance of side effects."
Dr. Vinks is leading two separate multicenter studies on the drug risperidone (Risperdal"). "Although more than 80 percent of children with pervasive development disorder receive risperidone, nothing is known about optimal dosing in children," Dr. Vinks notes. Pervasive development disorder (PDD) includes autism, related conditions and pervasive development disorder not otherwise specified (PDD-NOS).
Tailoring Doses
"Children who metabolize the drug slowly, so that more of it stays in their system, should receive lower doses than those who metabolize and get the drug out of their system more quickly," Dr. Vinks explains. "The pharmacokinetic study is revealing large variabilities in how fast children absorb, break down and eliminate risperidone." Knowing how their patients metabolize drugs can help pediatricians tailor dosing to their patients' needs.
Building on that study is another project "designed to determine if known differences in genes influence drug metabolizing enzymes and receptors related to risperidone action," Dr. Vinks says. "Do differences in these genes change the concentration of risperidone in the blood over time and influence clinical response and the chance of developing side effects to risperidone?" These are among the research questions the risperidone pharmacogenetics study addresses.
Predictive Medicine
The immunosuppressive drugs that children who have received organ transplantation must take lifelong to suppress their own immune reaction to transplants are potent and often have serious side effects. The drug mycophenolate mofetil (MMF, CellCept") shows large variations in how patients handle this drug when used with other standard immunosuppressive agents in children receiving kidney transplants, Dr. Vinks explains. He is leading a study to establish computer models for using MMF in pediatric kidney transplant patients.
The study will look at the way patients convert MMF in their bodies and how this affects their immune systems. Dr. Vinks and colleagues hope to develop predictive models to help correlate drug dosing regimens with early and long-term outcomes.
As computer models are developed, they also will be implemented by the Genetic Pharmacology Service (GPS) at Cincinnati Children's. "The method of combining genetic testing and population models for individualized dosing offered by GPS is new and unique throughout the country, and especially in pediatrics," Dr. Vinks says.
Here to Stay
His interest in developing models for personalized dosing led Dr. Vinks, who was born and raised in the Netherlands, to make his first foray to North America. In 1980, he accepted a scholarship at the University of Toronto to study with Werner Kalow, MD, who was doing pioneering work in phenotyping, characterizing patients who reacted differently to certain drugs.
Dr. Vinks returned to his homeland to work in pharmacology and clinical toxicology. His interests in pediatrics, population pharmacokinetics and pharmacogenetics, however, led him to Cincinnati. His work here and his growing attachment to the city and its vibrant arts community have kept him and his family here.
Dr. Vinks is professor of pediatrics in the Division of Clinical Pharmacology. Recent articles include a study of pharmacokinetic/pharmacodynamic modeling of antibacterials, published in Clinical Pharmacokinetics (44[2]:201-210, 2005 November) and a review of the cost-effectiveness of therapeutic drug monitoring, published in Therapeutic Drug Monitoring (27[1]:10-17, 2005 February).
