Clinical Pharmacology

Significant Accomplishments

NIH Training Grant 

We were awarded the first pediatric clinical and developmental pharmacology training grant (T32) from the National Institutes of Health.  This postdoctoral program will train the next generation of clinical investigators to assume leadership roles in developing innovative approaches that will enhance pediatric therapeutics.  Many medicines have not been scientifically evaluated for use in children and are either used unlicensed or in an off-label manner. In addition, far fewer medicines have been developed specifically to treat childhood diseases. One of our major goals is to provide research support and training that enhances the knowledge of residents, fellows and faculty about use of medications.

Individualized Therapies in Transplantation, Rheumatology and Anesthesiology 

Our investigators seek to better understand the dose-concentration-response and adverse-events relationships of immunosuppressive drugs in pediatric patients receiving organ transplants.  Immune suppressing therapies have led to unprecedented short-term patient and graft survival, but long-term survival rates remain suboptimal. Our ongoing research, funded through the National Institutes of Health and other sources, seeks to identify pharmacokinetic, pharmacodynamic and pharmacogenetic factors to explain differences in adverse events and clinical response in transplant patients. Our work includes studying the age-dependent disposition of mycophenolic acid in pediatric renal transplant recipients and children with lupus using newly discovered genetic polymorphisms. Our data will help develop web-based “dashboards” and dosing algorithms to allow personalized dose tailoring.

We also have finalized an important study in morbidly obese adolescents identifying pharmacokinetic, pharmacodynamic and pharmacogenetic factors that will allow personalized propofol anesthesia during bariatric surgery. As part of our personalized pain initiative, we work with colleagues in the Department of Anesthesia on novel pharmacological approaches that use the patient’s drug metabolizing genotype and phenotype to manage pain with morphine and related drugs, reduce adverse events and avoid clinically significant drug/drug interactions.

Pharmacometrics and Genetic Pharmacology Programs 

A pharmacometrics program was established to provide an academic training program that enables students, fellows and junior faculty to gain expertise in pharmacokinetic/pharmacodynamic modeling and simulation as part of clinical trial design, data analysis and individualized dosing algorithm development. Several clinical faculty and students from across the medical campus participate in the program.

We also continue to work with the Genetic Pharmacology Service, the first of its kind in a pediatric institution. This service is a first step toward personalized medicine for neuropsychiatric and anticoagulation drug therapy. Our research focuses on genotyping-phenotyping studies of neuropsychiatric drugs such as risperidone and warfarin. We develop computerized decision support systems that integrate evidence-based medicine, patient genotypes and phenotypes, as well as drug pharmacology and environmental factors.