Hideki Hirabayashi

TL;DR: In this article, DNA/RNA heteroduplex oligonucleotides conjugated to cholesterol or α-tocopherol at the 5′ end of the RNA strand reach the central nervous system (CNS) after subcutaneous or intravenous administration in mice and rats.

TL;DR: It is speculated that clinically used P-gp inhibitors do not cause DDI at the human BBB, because none of the compounds studied showed [I,unbound/Ki] values of >1 at therapeutic doses.

TL;DR: The in vitro metabolism of 14C-labeled TAK-438 was primarily metabolized by multiple metabolizing enzymes including CYP3A4, CYP2B6, CyP2C19, CYp2D6, and a non-CYP enzyme SULT2A1, and the influence of the CYP 2C19 genotype status on gastric acid suppression post TAK -438 dosing could be small.

TL;DR: An in vitro P-gp inhibition assay was designed and the appropriate risk criteria for P-GP-mediated DDI at the drug discovery stage was determined and it was indicated that ER is a highly sensitive parameter that can be used for the degree of P- gp inhibition.

TL;DR: The utility of PXB mice in predicting human PK parameters is demonstrated, with a higher predictability for CLt and Vdss values than the other animal models.