Quantitative prediction of bioavailability and drug-drug interactions of orally administered drugs

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460204
• 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): 2014-04-01 – 2017-03-31
• Keywords: 経口投与 / バイオアベイラビリティ / 薬物相互作用 / 定量的予測

Outline of Final Research Achievements

The present study aimed to improve a model to quantitatively predict the bioavailability and drug-drug interactions for orally administered CYP3A substrates. Alprazolam (ALP), midazolam (MDZ) and triazolam (TRZ) were used as CYP3A substrates, and ritonavir (RIT) and erythromycin (ERY) were used as CYP3A inhibitors. Metabolic and inhibition parameters of those drugs were obtained in in vitro studies. Transfer parameters in the intestinal epithelial cells were also estimated in vitro using Caco-2 cells. The obtained parameters were incorporated into an ITAM-PK model to predict the oral bioavailability of ALP, MDZ and TRZ, and also interactions between CYP3A substrates and CYP3A inhibitors.

Free Research Field

薬物動態学