Alexander Morin, Michael Christie, Eve Damiano, Maria L Maccecchini
{"title":"新型结晶邦坦肽在小鼠、狗和人体内的药代动力学。","authors":"Alexander Morin, Michael Christie, Eve Damiano, Maria L Maccecchini","doi":"10.3390/biom15091299","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 9","pages":""},"PeriodicalIF":4.8000,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467374/pdf/","citationCount":"0","resultStr":"{\"title\":\"Pharmacokinetics of Novel Crystalline Buntanetap in Mice, Dogs, and Humans.\",\"authors\":\"Alexander Morin, Michael Christie, Eve Damiano, Maria L Maccecchini\",\"doi\":\"10.3390/biom15091299\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":8943,\"journal\":{\"name\":\"Biomolecules\",\"volume\":\"15 9\",\"pages\":\"\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2025-09-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467374/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biomolecules\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.3390/biom15091299\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomolecules","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3390/biom15091299","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Pharmacokinetics of Novel Crystalline Buntanetap in Mice, Dogs, and Humans.
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.
BiomoleculesBiochemistry, 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.