以家蚕为动物模型,评估抗癌药物伊马替尼的体内药代动力学研究。

IF 1.9 Q3 PHARMACOLOGY & PHARMACY Drug Discoveries and Therapeutics Pub Date : 2024-09-19 Epub Date: 2024-08-18 DOI:10.5582/ddt.2024.01040
Takeo Yasu, Yasuhiko Matsumoto, Takashi Sugita
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引用次数: 0

摘要

伊马替尼是一种口服分子靶向疗法,是一种酪氨酸激酶抑制剂。蚕是一种很有前景的实验模型,可用于阐明各种化合物的药代动力学和毒性特征。本研究旨在建立一个实验范例,研究伊马替尼在蚕体内的药代动力学。通过比较分析蚕、人、小鼠和大鼠的伊马替尼药代动力学参数,发现蚕和人在达到最大浓度的时间(Tmax)和表观清除率值方面有相似之处。然而,蚕和人的消除半衰期(t1/2)和表观分布容积的差异分别保持在 5 倍和 4 倍的范围内。重要的是,在伊马替尼研究中,小鼠的药代动力学参数比大鼠更接近人类。此外,蚕和小鼠表现出相似的Tmax和t1/2值。这项研究强调了蚕在药代动力学研究中作为研究伊马替尼代谢的宝贵工具的潜力。此外,它还强调了蚕在阐明各种分子靶向药物的药代动力学参数方面的适用性,从而促进了药物开发和评估的进步。
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Evaluation of in vivo pharmacokinetic study of the anti-cancer drug imatinib using silkworms as an animal model.

Imatinib is an oral molecular targeted therapy that acts as a tyrosine kinase inhibitor. Silkworms present a promising experimental model for elucidating the pharmacokinetic and toxicity profiles of various compounds. This study aimed to establish an experimental paradigm for investigating the pharmacokinetics of imatinib in silkworms. A comparative analysis of imatinib pharmacokinetic parameters across silkworms, humans, mice, and rats revealed similarities in time to maximum concentration (Tmax) and apparent clearance values between silkworms and humans. However, differences in elimination half-life (t1/2) and apparent volume of distribution between silkworms and humans remained within 5- and 4-fold ranges, respectively. Importantly, mice demonstrated pharmacokinetic parameters closer to those of humans than rats during imatinib studies. Additionally, silkworms and mice exhibit similar Tmax and t1/2 values. This study highlights the potential of silkworms as valuable tools for investigating imatinib metabolism in pharmacokinetic studies. Furthermore, it underscores the applicability of silkworms in elucidating the pharmacokinetic parameters of various molecular-targeted drugs, thus facilitating advancements in drug development and evaluation.

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来源期刊
Drug Discoveries and Therapeutics
Drug Discoveries and Therapeutics PHARMACOLOGY & PHARMACY-
CiteScore
3.20
自引率
3.20%
发文量
51
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