Alexander "Sander" A. Vinks, PharmD, PhD, FCP
Electronic Health Record (EHR)-embedded Decision Support Platform for Individualized Precision Drug Treatment in Neonates
In studies funded by the Ohio Third Frontier and the Gerber Foundation, Sander Vinks, PharmD, PhD, FCP, and a team of investigators from the Divisions of Neonatology, Pulmonary Biology, Pharmacy, Information Services, Biomedical Informatics, and Pain and Palliative Medicine as well as the Clinical Mass Spectrometry Laboratory implemented a morphine individualized precision dosing tool into workflows of neonatal prescribing clinicians. An ongoing study seeks to support and improve neonatal pain management by implementing decision support for morphing precision dosing. The study is measuring the implementation effects by usage statistics and by comparing prescribing patterns to historical patterns from prior to implementation. We also continue to collect pain and sedation scores, vital signs, and predicted and measured morphine concentrations, comparing prescribing patterns to historical patterns from prior to implementation.
Chie Emoto, PhD
Physiologically-based pharmacokinetic (PBPK) model of morphine and developmental changes in transporter expression in neonates
Chie Emoto, PhD, received an award of a R21 grant from NICHD to improve our understanding of morphine pharmacokinetics and dosing in neonates. Studies included pharmacogenetic analysis of the organic cation transporter 1 (OCT1) transporter genotype, an important contributor to differences in morphine pharmacokinetics. In addition, in vitro studies revealed the ontogeny of the OCT1 transporter and of morphine’s main drug metabolizing pathway through the UDP glucuronosyltransferase (UGT2B7) enzyme. This project started with a CCTST T1 pilot grant. The research team successfully developed a neonatal morphine physiologically-based pharmacokinetic (PBPK) model that incorporates OCT1 genotype and related developmental protein expression trajectories. In addition, the team implemented patient-specific information for prediction of morphine disposition in individual patients. Clinical Pharmacology and Therapeutics, the leading journal of the American Society of Clinical Pharmacology and Therapeutics (ASCPT), recently published two manuscripts of research findings.
Dr. Emoto also received a CCRF Research Innovation Pilot grant to develop a tacrolimus PBPK model to optimize immunosuppressive therapy in pediatric kidney and liver transplant recipients. The multidisciplinary team consists of investigators from the Divisions of Nephrology; Gastroenterology, Hepatology and Nutrition; Biomedical Informatics, and the Discover Together Biobank. Preliminary data regarding the PBPK modeling of tacrolimus received publication in CPT: Pharmacometrics & Systems Pharmacology, which is one of the official journals of ASCPT.
Min Dong, PhD
Min Dong, PhD, works with investigators in the Division of Hematology on precision dosing studies of hydroxyurea in patients with sickle cell anemia (SCA). Currently two ongoing prospective trials are: Therapeutic Response Evaluation and Adherence Trial (TREAT), and the hydroxyurea optimization through precision study (HOPS). Another initiative focuses on dose optimization of hydroxyurea in children after total pancreatectomy with islet auto-transplantation (TPIAT) with investigators from the Pancreas Care Center. Dr. Dong continues to provide pharmacometric services in support of multiple research projects in collaboration with investigators in the Divisions of Anesthesiology, Research in Patient Services, and Audiology. She is also a leader in the Cincinnati Pharmacometrics Center of Excellence program providing high level pharmacometrics expertise for pediatric study design optimization, clinical trial simulation, pediatric dose selection optimization, and protocol development for pharmacokinetic (PK) and pharmacodynamic (PD) studies for FDA submission by outside sponsors.Genetic Pharmacology Service and Pharmacogenomics Implementation Research Center (Precise)
Members of the division participate in the genetic pharmacology service (GPS) established in 2004 as a multidisciplinary program supported by the Divisions of Human Genetics, Pharmacy, and Research in Patient Services. Members of the GPS team worked with the associate dean for research and innovation at the James Winkle College of Pharmacy at the University of Cincinnati to establish a new pharmacogenomics and personalized healthcare track within the master of science in pharmaceutical sciences degree.
With support from the Center for Pediatric Genomic, Laura Ramsey, PhD, brought together a multidisciplinary team of investigators from the Divisions of Research in Patient Services, Nephrology, Pharmacy, Human Genetics, and the James M. Anderson Center for Health Systems Excellence to conduct prospective studies of CYP3A5-guided individualized tacrolimus dosing to improve the outcomes for pediatric transplant patients.
NIH T32 Pediatric Clinical Pharmacology Postdoctoral Training Program
The Division of Clinical Pharmacology is proud of its fellowship program in pediatric clinical pharmacology which is one of only five sites in the US with an active program supported by the National Institute of Child Health and Development (NICHD). The goal of the postdoctoral program is to train clinical investigators to assume leadership roles in improving pediatric therapeutics. Many medicines are not studied for use in newborns and children, and few medicines are specifically developed to treat childhood diseases. Our program supports and trains fellows in applying pharmacokinetics and pharmacogenetics/genomics principles as part of study design as well as precision medicine approaches. The National Institute of Mental Health (NIMH) supported our program to pilot the training of the next generation of pediatric psychiatrists in early stage pediatric clinical trial design and PK/PD bridging studies. We actively participate in the Adult and Pediatric Clinical Pharmacology Training Network established by NICHD, and the National Institutes of General Medical Sciences (NIGMS), as a strategic initiative to increase the pool of well-trained pediatric clinical pharmacologists.NIH T32 Pediatric Clinical Pharmacology Postdoctoral Training Program
The Division of Clinical Pharmacology is proud of its fellowship program in pediatric clinical pharmacology which is one of only five sites in the US with an active program supported by the National Institute of Child Health and Development (NICHD). The goal of the postdoctoral program is to train clinical investigators to assume leadership roles in improving pediatric therapeutics. Many medicines are not studied for use in newborns and children, and few medicines are specifically developed to treat childhood diseases. Our program supports and trains fellows in applying pharmacokinetics and pharmacogenetics/genomics principles as part of study design as well as precision medicine approaches. The National Institute of Mental Health (NIMH) supported our program to pilot the training of the next generation of pediatric psychiatrists in early stage pediatric clinical trial design and PK/PD bridging studies. We actively participate in the Adult and Pediatric Clinical Pharmacology Training Network established by NICHD, and the National Institutes of General Medical Sciences (NIGMS), as a strategic initiative to increase the pool of well-trained pediatric clinical pharmacologists.Genetic Pharmacology Service and Pharmacogenomics Implementation Research Center (Precise)
Members of the division participate in the genetic pharmacology service (GPS) established in 2004 as a multidisciplinary program supported by the Divisions of Human Genetics, Pharmacy, and Research in Patient Services. Members of the GPS team worked with the associate dean for research and innovation at the James Winkle College of Pharmacy at the University of Cincinnati to establish a new pharmacogenomics and personalized healthcare track within the master of science in pharmaceutical sciences degree.
With support from the Center for Pediatric Genomic, Laura Ramsey, PhD, brought together a multidisciplinary team of investigators from the Divisions of Research in Patient Services, Nephrology, Pharmacy, Human Genetics, and the James M. Anderson Center for Health Systems Excellence to conduct prospective studies of CYP3A5-guided individualized tacrolimus dosing to improve the outcomes for pediatric transplant patients.
