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Drug Distribution: Tissue Binding01:21

Drug Distribution: Tissue Binding

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Upon entering the systemic circulation, drugs can distribute into the interstitial and intracellular fluid of various tissue cells. This distribution is facilitated by the binding of drugs to different cellular components within tissues, which may lead to drug accumulation in specific areas. Drugs bound to tissue components serve as reservoirs that release free drugs back into the system, prolonging the drug's overall action. However, this accumulation can also result in local toxicity.
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Pharmacokinetics in Pediatric Patients: Drug Distribution01:17

Pharmacokinetics in Pediatric Patients: Drug Distribution

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Drug distribution in the pediatric population exhibits unique challenges and considerations due to the physiological differences between children, particularly neonates and infants, and adults. A crucial aspect of pediatric pharmacology is understanding how these differences impact the pharmacokinetics of various drugs, necessitating age-specific dosing strategies to ensure efficacy and safety.Neonates and infants have a higher total body water content, ~75%–90% of their body weight,...
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Measurement of Bioavailability: Pharmacokinetic Methods01:30

Measurement of Bioavailability: Pharmacokinetic Methods

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Pharmacokinetics is a vital branch of pharmacology that examines how drugs are absorbed, distributed, metabolized, and excreted by the body. Two key methodologies in pharmacokinetics are plasma drug concentration studies and urinary drug excretion analyses, both of which provide critical insights into a drug's therapeutic efficacy and bioavailability.Plasma Drug Concentration-Time StudiesPlasma drug concentration-time studies involve analyzing blood samples at specific intervals to quantify...
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Measurement of Bioavailability: Pharmacodynamic Methods01:20

Measurement of Bioavailability: Pharmacodynamic Methods

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Pharmacodynamic methods provide insights into a drug's effects on physiological processes over time and play a crucial role in understanding bioavailability and therapeutic efficacy. These methods can be broadly classified into acute pharmacological and therapeutic response approaches, each with distinct mechanisms and applications.The acute pharmacological response method directly correlates a drug's physiological effects, such as ECG or pupil diameter changes, to its time course in the body.
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Pharmacokinetics: Overview01:10

Pharmacokinetics: Overview

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Pharmacokinetics is a scientific discipline that focuses on the journey of a drug within the body, encompassing four key stages: absorption, distribution, metabolism, and elimination. The first stage, absorption, involves the drug's transfer into the bloodstream. Several factors dictate the extent and speed of this process. For example, the liver often metabolizes oral drugs before they reach systemic circulation, leading to only partial absorption. In contrast, intravenous (IV)...
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Compartment Models: Two-Compartment Model01:20

Compartment Models: Two-Compartment Model

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The two-compartment model divides the body into central and peripheral compartments to account for varying blood perfusion rates among organs and tissues, affecting drug distribution. The central compartment includes blood and highly perfused tissues with rapid drug distribution, while the peripheral compartment contains tissues with slower drug distribution. After a single IV bolus dose, the drug concentration is high in plasma and low in tissues. The drug distribution between compartments...
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Investigations on the GaIII Complex of EOB-DTPA and Its 68Ga Radiolabeled Analogue
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Trityl OXO71薬物動態およびカニクイザルにおける分布

Christopher D Kroenke1, Irene Canavesi2, Jenna N Castro3

  • 1Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.

Magnetic resonance in medicine
|December 16, 2025
PubMed
まとめ

TritylラジカルOXO71を用いた電子常磁性共鳴酸素イメージング（EPROI）はカニクイザルにおいて安全である。本研究は、ヒトにおけるEPROIの最適化に不可欠な薬物動態および組織分布データを提供する。

キーワード:
電子常磁性共鳴非ヒト霊長類酸素イメージング薬物動態トリチルラジカル

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科学分野:

  • 生物医学イメージング
  • 医用物理学
  • 薬理学

背景:

  • 電子常磁性共鳴酸素イメージング（EPROI）は、生体内の酸素分圧（pO2）を定量化する。
  • OXO71はEPROIに使用されるトリチルラジカルであり、以前は小型動物の研究で応用されていた。
  • EPROIをヒトでの使用に移行するには、ヒトに類似した大型動物モデルでの最適化が必要である。

研究 の 目的:

  • カニクイザルにおける静脈内投与後のOXO71の薬物動態を特徴づけること。
  • カニクイザルにおけるOXO71の組織分布を決定すること。
  • 霊長類モデルにおけるEPROIのためのOXO71の安全性と実現可能性を評価すること。

主な方法:

  • 3匹のカニクイザルに92 μmol/kgのOXO71を10分かけて静脈内ボーラス注射した。
  • 投与後2時間まで血漿および尿サンプルを採取した。
  • 2回目の投与後、動物を安楽死させ、EPRイメージングを用いて組織分布を評価した。

主要な成果:

  • 血漿中OXO71は二相性クリアランスを示し、初期および終末半減期はそれぞれ12.4 ± 1.2分および67.7 ± 8.9分であった。
  • 脳を除くほとんどの組織でかなりの濃度のOXO71が検出された。
  • 有害な生理学的影響は観察されず、毒性が低いことが示された。

結論:

  • OXO71を用いたEPROIは、霊長類において安全で忍容性が良好である。
  • 薬物動態および組織分布データは、大型動物およびヒトにおけるEPROIの投与量とタイミングを決定する上で役立つ。
  • これらの発見は、臨床応用におけるOXO71ベースのEPROIのさらなる開発を支持するものである。