Left to Right: S Saldana, T Fukuda, S Vinks, M Spigarelli
The Division’s mission is to conduct state-of-the-art Phase I - III clinical pharmacology studies that conform to GCP/ICH regulatory requirements in a safe, effective and timely fashion to produce new knowledge to enable optimal use of medications in newborns, children and adolescents. Our faculty is particularly interested in pharmacogenetics (PG), and population pharmacokinetic (PK)-pharmacodynamic (PD) modeling, and has extensive expertise in clinical trial design and simulation. We have ongoing studies in the pharmacogenetics (PG) of warfarin, and risperidone, the PK/PD and PG of mycophenolic acid (MMF, CellCept®) in transplant patients (with Nephrology), and in children with Lupus (with Rheumatology), and propofol PK/PG dose optimization studies in morbidly obese patients (with Anesthesia and Surgery).
Alexander A. Vinks, PharmD, PhD
Dr. Vinks was awarded the first pediatric T32 training grant in Clinical and Developmental Pharmacology from NICHD to train the next generation of pediatric clinical pharmacologists. Dr. Vinks also serves as president of the International Association for Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT). In this role he initiated clinical pharmacology and TDM related educational activities across the world by facilitating regional meetings in China, India and South America. As principal investigator of a TEENS-LAB ancillary pharmacokinetic, pharmacodynamic and pharmacogenetics study of propofol in morbidly obese patients he and his team successfully completed this study. The project was supported by the translational research initiative (TRI). The purpose of the study is to develop a personalized dosing algorithm for propofol use in bariatric surgery patients.
Tsuyoshi Fukuda, PhD
Dr. Fukuda was invited for presentation of the Division’s ongoing research on the Pharmacokinetics (PK) and Pharmacodynamics (PD) and Pharmacogenetics (PG) of Mycophenolate Mofetil in pediatric kidney transplant patients and childhood-onset Systemic Lupus Erythematosus (cSLE) at a FDA expert meeting on biomarker development. In addition, his work was selected for presentation at the Annual meeting of the American Society of Clinical Pharmacology and Therapeutics (Dallas, March 2011) and at Showa Pharmaceutical University in Japan.
Shannon N. Saldaña, PharmD, MS
Dr. Saldaña completed her warfarin pharmacogenetic study supported by a T1 Translational Research Award through the University of Cincinnati Center for Clinical and Translational Science (CCTST). The goal is to develop a pediatric warfarin dosing algorithm that incorporates clinical information and CYP2C9 and VKORC1 genotypes. She also completed her pharmacokinetics and pharmacogenetic study in risperidone-treated children and adolescents with psychiatric or neurodevelopmental disorders with support from the Clinical Research Feasibility Funds Program (CREFF). This work builds on risperidone studies performed by our PPRU in the past. The results will be used to design a proof-of-concept prospective trial to test PK/PG-guided dosing in psychiatric patients initiated on risperidone treatment.
Michael G. Spigarelli, MD, PhD
Dr. Spigarelli served as the chair of the Special Population Section of the American Society for Clinical Pharmacology and Therapeutics (ASCPT) and as a board member of the American Board of Clinical Therapeutics chairing the Certification Examination Subcommittee responsible for designing and administering the national certification examination. He also serves as the chair of the Adolescent Prioritization Committee for the Best Pharmaceuticals for Children Act (BPCA). His research involves a variety of different projects from directing the Cincinnati Genomic Control Cohort Project to working to understand the role adverse events such as weight gain and hormonal imbalance play in susceptible individuals and how that can provide insight regarding the underlying physiologic and pharmacologic mechanisms involved.
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.