Publications by authors named "Tomomi Taniguchi-Takizawa"
Article Synopsis
- This study estimates the role of flavin-containing monooxygenase 3 (FMO3) in drug N-oxygenation by comparing metabolic clearance values of model drugs at different pH levels.
- It was found that metabolic clearance for certain drugs at pH 8.4 was significantly higher than at pH 7.4, while midazolam showed the opposite trend.
- The findings indicate that comparing clearance values across pH levels can help predict FMO3's impact on N-oxygenations in new drug development, particularly for drugs with pKa values over 8.4.
Article Synopsis
- The study focused on the base dissociation constants (pKa) of 30 model drugs to assess how flavin-containing monooxygenases (FMOs) influence drug metabolism, particularly in N-oxygenations.
- It revealed that the effectiveness of FMOs in metabolizing these drugs could be underestimated in certain research conditions commonly used during drug development.
- The findings suggest that a molecular descriptor such as the base dissociation constant can help predict metabolic sites and the involvement of FMOs in drug metabolism, providing a simpler method to estimate the potential contributions of these enzymes.
Benzydamine is an anti-inflammatory drug that undergoes flavin-containing monooxygenase (FMO)-dependent metabolism to benzydamine N-oxide; however, benzydamine N-demethylation is also catalyzed by liver microsomes. In this study, benzydamine N-oxygenation and N-demethylation mediated by liver microsomes from rats, dogs, monkeys, and humans were characterized comprehensively. Values of the maximum velocity/Michaelis constant ratio for benzydamine N-oxygenation by liver microsomes from dogs and rats were higher than those from monkeys and humans, despite roughly similar rates of N-demethylation in the four species.
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