Tomoyuki Mizuno, PhD

My research has focused on applying pharmacokinetic-pharmacodynamic (PK / PD) modeling, pharmacometrics, and quantitative pharmacology to develop and implement personalized drug dosing strategies in pediatric patients. This approach to therapeutic optimization is now being coined as “model-informed precision dosing (MIPD)” and is part of a wider context of precision medicine.

Most medical treatments on the market come with dosage recommendations for the average patient. However, with many medications, an optimal dose varies among patients due to substantial variability in drug exposure, efficacy and toxicity. A "one-size-fits-all" approach works for some patients but not for others. Providing the appropriate dose is particularly challenging in children, especially in neonates and infants who experience rapid dynamic changes in their body size and physiological organ functions.

Our overarching goal is to facilitate and improve optimal personalized use of medications in children by using PK / PD principles and quantitative approaches with data-driven and mechanism-based mathematical modeling and simulation of drug response.

With our previous collaborative projects, we developed and implemented a MIPD strategy for mTOR inhibitor, sirolimus in pediatric patients with various diseases, such as vascular anomalies and acute lymphoblastic leukemia. Our studies successfully characterized and modeled the developmental changes in drug elimination capacity to predict drug exposure to sirolimus in children and infants. These models are used to design age-appropriate dosing regimens and implement real-time dose personalization in multiple clinical trials and routine clinical care.

Our group also found a new treatment protocol of methadone to expedite the achievement of adequate disease remission in infants with neonatal opioid withdrawal syndrome (NOWS) based on the model-informed simulation of drug exposure. We developed the PK/PD model for buprenorphine to predict disease progression and treatment outcomes in infants with NOWS. We also developed the age-appropriate dosing model for newborns and infants who need the drug milrinone to prevent low cardiac output syndrome after receiving cardiac surgery, including acute kidney injury (AKI) cases.

I also serve as a member of the Cincinnati Pharmacometrics Center of Excellence program providing strategic clinical pharmacology consulting and pharmacometrics services to help pharmaceutical and biotechnology companies seeking expertise to determine the optimal clinical trial design and pharmacometrics analysis as part of initial Pediatric Study Plans (iPSP) for FDA submission.

I have published over 55 peer-reviewed manuscripts and have presented more than 100 abstracts at national and international meetings. I’m an associate member of the Center for Addiction Research, University of Cincinnati College of Medicine, and a member of the Pharmacometrics Committee, the Therapeutic Drug Monitoring (TDM) of Biologics Committee and the Young Scientist Committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT). I have been a researcher for more than 12 years and began working at Cincinnati Children's in 2012.