Pharmacokinetics of Novel Crystalline Buntanetap in Mice, Dogs, and Humans.

IF 4.8 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Biomolecules Pub Date : 2025-09-10 DOI:10.3390/biom15091299
Alexander Morin, Michael Christie, Eve Damiano, Maria L Maccecchini
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引用次数: 0

Abstract

Buntanetap is an orally bioavailable small molecule that has been shown to improve cognitive function in patients with Alzheimer's and Parkinson's diseases and holds promise for use in other neurodegenerative conditions. Until now, a crystalline anhydrate (Form A) has been used in preclinical and clinical studies. However, a novel dihydrate crystal (Form B) was recently discovered, offering improved solid-state stability without compromising its absorption, systemic exposure, and metabolism. We sought to evaluate the pharmacokinetic (PK) profile of Form B and compare it to the well-characterized PK profile of Form A in a series of studies conducted in mice, dogs, and humans. Our data revealed that although the two forms are distinct and do not interconvert, they exhibit comparable PK profiles both within and across species. Consistent with previous reports, Form A and Form B alike reached fast peak plasma concentrations (<2 h), demonstrated efficient partitioning into brain tissue, and were fully cleared by 12 h post-dose. Furthermore, metabolic profiling showed that both forms produced identical PK profiles for the primary metabolites, N1- and N8-norbuntanetap, confirming that Form B retains the established metabolic characteristics of Form A. These findings support the continued development of Form B for future clinical use, as it combines enhanced solid-state stability with a preserved PK profile essential for buntanetap's therapeutic efficacy.

新型结晶邦坦肽在小鼠、狗和人体内的药代动力学。
Buntanetap是一种口服生物可利用的小分子,已被证明可以改善阿尔茨海默氏症和帕金森病患者的认知功能,并有望用于其他神经退行性疾病。到目前为止,晶体无水(形式a)已用于临床前和临床研究。然而,最近发现了一种新的二水合物晶体(形式B),在不影响其吸收、全身暴露和代谢的情况下,提供了更好的固态稳定性。我们试图评估形式B的药代动力学(PK)特征,并将其与形式A的药代动力学特征进行比较,在小鼠,狗和人类中进行了一系列研究。我们的数据显示,尽管这两种形式是不同的,不相互转换,它们在物种内和物种间都表现出可比的PK谱。与之前的报告一致,A型和B型的血浆浓度都达到了快速峰值(
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来源期刊
Biomolecules
Biomolecules Biochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
9.40
自引率
3.60%
发文量
1640
审稿时长
18.28 days
期刊介绍: Biomolecules (ISSN 2218-273X) is an international, peer-reviewed open access journal focusing on biogenic substances and their biological functions, structures, interactions with other molecules, and their microenvironment as well as biological systems. Biomolecules publishes reviews, regular research papers and short communications.  Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.
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