Quantitative prediction of oral bioavailability independent of metabolic pathway

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08423
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Kitasato University
• Principal Investigator: ITOH Tomoo 北里大学, 薬学部, 教授 (30223168)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 経口投与 / バイオアベイラビリティ / 薬物間相互作用 / 定量的予測

Outline of Final Research Achievements

ITAM-PK model was developed to quantitatively predict oral bioavailability and drug-drug interactions for orally administered CYP3A4 substrates. The present study aimed to apply the model to quantitatively predict the bioavailability and drug-drug interactions for the substrates that are metabolized by enzymes other than CYP3A4. Oral bioavailability of CYP1A2 substrates, tizanidine and theophylline, were reasonably well predicted. For propranolol, cellular binding of the substrate needs to be incorporated to predict oral bioavailability. Drug-drug interactions (DDI) between tizanidine and fluvoxamine, a CYP1A2 inhibitor, were quantitatively predicted very well. On the other hand, DDI between tizanidine and ciprofloxacin, another CYP1A2 inhibitor, was not well predicted.

Free Research Field

薬物動態学

Academic Significance and Societal Importance of the Research Achievements

試験管内の実験データをもとに、薬物を経口投与のバイオアベイラビリティや薬物間相互作用を定量的に予測することができれば、医薬品開発の無駄をなくし、ヒトに投与する前に薬物間相互作用を回避することが可能となる。