Min Dong, PhD

Dong’s research interests include quantitative clinical pharmacology, model informed dose optimization and clinical trial design. She works with investigators in the Division of Hematology on model-informed pharmacokinetically-guided precision dosing studies of hydroxyurea in patients with sickle cell anemia (SCA), and recently received a K01 to study hydroxyurea exposure in pregnant and lactating women with SCA using an in silico Physiologically-based Pharmacokinetic (PBKP) modeling approach. In addition, she continues to provide pharmacometric services in support of multiple funded research projects in collaboration with investigators in the Cancer and Blood Diseases Institute, the Divisions of Research in Patient Services, Audiology, Hospital Medicine and other clinical divisions. She is also a leader in the Cincinnati Pharmacometrics Center of Excellence program providing high level pharmacometric 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.

Tomoyuki Mizuno, PhD

Mizuno works with multiple clinical teams to develop and implement model-informed precision dosing (MIPD) strategies using pharmacokinetics and pharmacodynamics (PK/PD) and systems pharmacology modeling and simulation in patients of all ages, from neonates to adults. He and his team recently published an innovative research paper describing a physiology-based (PBPK) model for buprenorphine to investigate the effect of maturation of organ functions in neonates treated for neonatal opioid withdrawal syndrome (NOWS). This work was performed in collaboration with investigators in the Divisions of Neonatology and Pulmonary Biology. He works on multiple MIPD projects of anti-inflammatory biologics in pediatric patients with inflammatory bowel diseases in collaboration with investigators in the Division of Gastroenterology, Hepatology, and Nutrition. On an ongoing basis, his involvement in projects studying mTOR inhibitors, such as sirolimus and everolimus, is in collaboration with investigators in the Division of Neurology, Cancer and Blood Diseases Institute, and external collaborators. He is a leading member of the Cincinnati Pharmacometrics Center of Excellence providing strategic clinical pharmacology consulting and pharmacometrics services to support internal and external sponsors seeking expertise for optimal clinical trial design and pharmacometrics analysis as part of model-informed drug development (MIDD) programs and initial Pediatric Study Plan (iPSP) development for FDA submissions. His recent pharmacometrics project includes MIDD of mirdametinib using a mechanism-based PK/PD and disease progression model in adolescents and young adults with neurofibromatosis type 1 (NFL)-related plexiform neurofibromas. Lastly, he is a leader in the division’s PK-guided precision dosing service providing real-time PK assessment and personalized dosing recommendations using Bayesian approaches for various drugs, including immunosuppressants, biologics, and anti-infection medications.

Kana Mizuno, PhD

Mizuno’s research focuses on the development and implementation of model-informed precision dosing (MIPD) and pediatric clinical trial design based on quantitative clinical pharmacological approaches. She works with multiple investigators in the Division of Bone Marrow Transplantation and Immune Deficiency and the Cancer and Blood Diseases Institute on the development of MIPD dosing algorithms for patients undergoing stem-cell transplantation. An important highlight is the publishing of a recent manuscript in which Mizuno and the clinical team describe a unique population pharmacokinetics/pharmacodynamics modeling approach of eculizumab integrated with disease biomarkers in patients with severe transplant-associated thrombotic microangiopathy (TMA). This work carries great promise for improved patient recovery and survival. Mizuno continues to expand this research program with the recent development of a web-based dosing tool and eculizumab app for real time MIPD dose optimization. She also collaborates on projects with the Division of Neurology on the development of MIPD strategies for Childhood Absence Epilepsy treatments aiming to increase in the probability of treatment success. Mizuno serves as a leading expert and member of the Cincinnati Pharmacometrics Center of Excellence program. She provides pharmacometrics support for optimal pediatric clinical trial design, and first in human precision dosing simulations as part of model-informed drug development programs and in support of the development of initial Pediatric Study Plans (iPSP) for FDA submissions.

Laura Ramsey, PhD

Ramsey works closely with the Divisions of Human Genetics, the Center for Autoimmune Genomics and Etiology and the Division of Oncology to employ pharmacogenetics approaches in clinical and translational studies. Ramsey and collaborators from the Divisions of Research in Patient Services, Clinical Pharmacology and Biomedical Informatics created a webtool that informs clinicians about methotrexate pharmacokinetics for individual patients, mtxpk.org. She receives funding from the National Institute of Child Health and Development to study neuropsychiatric pharmacogenetics in pediatric patients with the University of Cincinnati Department of Psychiatry and Behavioral Neuroscience. Ramsey’s lab finding that pharmacogenetic variants influenced the response, toxicity and dosing of antidepressants (sertraline, citalopram and escitalopram) in children, prompted an update in clinical decision support with dosing guidelines through the Genetic Pharmacology Service to optimize dosing and potentially avoid side effects from these medications. The Genetic Pharmacology Service is a multidisciplinary team she co-leads to develop, interpret and implement pharmacogenetic tests in the electronic medical record. She also educates doctors, pharmacists, genetic counselors and nurses on when and how to use pharmacogenetic tests in the clinic.

Sonya Tang Girdwood, MD, PhD

Tang Girdwood is a faculty member in the Divisions of Clinical Pharmacology and Hospital Medicine and works closely with the Division of Critical Care Medicine and the Center for Acute Care Nephrology. During her fellowships in the Divisions of Hospital Medicine and Clinical Pharmacology, she built the infrastructure to study beta-lactam antibiotic pharmacokinetics and pharmacodynamics in critically ill children. She utilizes pharmacometrics methods to characterize the variability of beta-lactam concentrations at a population level and to identify patient and clinical factors that contribute to the variability. She also evaluates the pharmacokinetic profiles and pharmacodynamics of beta-lactams in individual patients on extracorporeal life support, including Molecular Adsorbent Recirculation System (MARS) therapy, Extracorporeal Membrane Oxygenation (ECMO) therapy and Continuous Renal Replacement Therapy (CRRT). She expanded her research to evaluate relationships between beta-lactam concentrations and toxicity, including acute kidney injury. She initially received funding from the K12 Child Health Research Career Development Award in her first year as faculty. She recently received an R35 Maximizing Investigator’s Research Award from NIGMS to continue her work in studying antibiotic precision dosing in critical illness. She clinically works on the Division of Hospital Medicine general pediatric teams and complex care team.

Alexander Sander A Vinks, PharmD, PhD, FCP

In studies with funding from the Ohio Third Frontier and the Gerber Foundation, Vinks and a multidisciplinary team of investigators from the Divisions of Neonatology, Pulmonary Biology, Clinical Pharmacology, Information Services, Biomedical Informatics, the Pain Management Center and Pediatric Palliative Care as the Clinical Mass Spectrometry Laboratory implemented a morphine individualized precision dosing tool into workflows of neonatal prescribing clinicians. This initiative seeks to support and improve neonatal pain and sedation management by implementing decision support at the bedside for morphine and midazolam precision dosing. The study measures the implementation effects by usage statistics and by comparing prescribing patterns to historical patterns from prior to implementation.

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 pediatrics specific 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. There are no studies of many medicines for use in newborns and children, and there are few medicines specifically developed to treat childhood diseases. Our program supports and trains fellows in applying pharmacokinetics and pharmacogenetics / genomics principles as part of study design, model-informed drug development as well as precision medicine approaches. We actively participate in the NICHD and the National Institutes of General Medical Sciences (NIGMS) Adult and Pediatric Clinical Pharmacology Training Network and the newly established Maternal and Pediatric Precision in Therapeutics (MPRINT) program as a strategic initiative to increase the pool of well-trained pediatric clinical pharmacologists.

Pharmacometrics Center of Excellence

Our program continues to experience significant growth with our expert consulting offerings, increased project diversity, and client base, including in-house, biopharmaceutical, biotechnology, and specialty pharmaceutical companies seeking expertise to determine optimal clinical trial design and pharmacometrics analysis as part of FDA pediatric investigational plans and Model-Informed Drug Development (MIDD) programs. Our center offers strategic clinical pharmacology consulting and pharmacometric support services to help clients improve pediatric drug development and regulatory decision-making throughout the clinical development process to increase the success rate of pediatric and adult drug studies. Our team provides expertise in clinical pharmacology, PK / PD support and data analysis, model-informed drug development strategies, PK / PD modeling and simulation, study design optimization, clinical trial simulation, and the development of model-informed precision dosing strategies.

Genetic Pharmacology Service and Pharmacogenetics Implementation Research Center Precise

Division members Vinks, Sonya Tang Girdwood, MD, PhD, and Laura Ramsey, PhD, co-lead the Genetic Pharmacology Service (GPS) with Tracy Glauser, MD. The GPS established in 2004 as a multidisciplinary program involving the Divisions of Human Genetics, Neurology, Clinical Pharmacology, and Research in Patient Services. This year, Ramsey presented about the program at the American Academy of Child and Adolescent Psychiatry, Association for Molecular Pathology, Precision Medicine World Conference, and Pediatric Academic Societies annual meetings, as well as the Mayo Clinic Department of Psychiatry Rounds for several US hospitals. Ramsey also presented to several local groups, including the Division of Child and Adolescent Psychiatry and the UC College of Pharmacy Students. This year, the GPS formed nearly 2,500 tests, implemented NUDTI5 testing for thiopurines, and updated reporting of CYP2D6 duplications to improve description of CYPD2D6 ultrarapid metabolizers.