When to consider intra-target microdosing: physiologically based pharmacokinetic modeling approach to quantitatively identify key factors for observing target engagement

Intra-Target Microdosing (ITM), integral to Phase 0 clinical studies, offers a novel approach in drug development, effectively bridging the gap between preclinical and clinical phases. This methodology is especially relevant in streamlining early drug development stages. Our research utilized a Physiologically Based Pharmacokinetic (PBPK) model and Monte Carlo simulations to examine factors influencing the effectiveness of ITM in achieving target engagement. The study revealed that ITM is capable of engaging targets at levels akin to systemically administered therapeutic doses for specific compounds. However, we also observed a notable decrease in the probability of success when the predicted therapeutic dose exceeds 10 mg. Additionally, our findings identified several critical factors affecting the success of ITM. These encompass both lower dissociation constants, higher systemic clearance and an optimum abundance of receptors in the target organ. Target tissues characterized by relatively low blood flow rates and high drug clearance capacities were deemed more conducive to successful ITM. These insights emphasize the necessity of taking into account each drug’s unique pharmacokinetic and pharmacodynamic properties, along with the physiological characteristics of the target tissue, in determining the suitability of ITM

Toward the Creation of Highly Active Photocatalysts That Convert Methane into Methanol

Methane exists abundantly around Japan as methane hydrate. As the effective use of such methane, the conversion of methane into methanol has recently attracted much attention. Photocatalytic reaction is one of the methods which convert methane into methanol without using much energy. However, it is indispensable to improve the photocatalytic activity for their practical use. Our group has attempted to improve the activity of mesoporous tungsten trioxide and titanium dioxide (m-WO3 and m-TiO2) photocatalysts, which convert methane into methanol, by loading the ultrafine metal clusters as cocatalyst on the photocatalysts. As a result, we have succeeded in loading ultrafine metal-cluster cocatalysts onto m-WO3 and m-TiO2 and thereby improving their photocatalytic activity. Our study also demonstrated that the kind of metal element suitable for each photocatalyst depends on the kind of the photocatalysts, and thereby it is important to select the metal clusters suitable for each photocatalyst for improving its photocatalytic activity

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ミンカン ダンタイ アーカイブズ ノ セイリ ヘンセイ キジュツ ノ ココロミ ニッポン リッコウカイ ナガタ シゲシ ブンショ オ ジレイ ニ

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ニホン ニオケル ミンカン シリョウ ノ ゲンジョウ ト コレカラ ノ カダイ

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クボ トオル セバタ ハジメ コッカ ト ヒミツ カクサレル コウブンショ

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