{"title":"尺寸依赖性肾过滤模型解释了功能纳米粒子的人体药代动力学:SPAGOPIX-01 临床试验。","authors":"","doi":"10.1016/j.nano.2024.102774","DOIUrl":null,"url":null,"abstract":"<div><p>The pharmacokinetics in patients dosed with the nanoparticle-based MRI contrast agent SN132D is explained by a size dependent clearance mechanism and this behavior was modeled numerically. Blood samples from 14 patients were analyzed for silicon (a component of the nanoparticle) by ICP-OES. The pharmacokinetic model has only one free parameter and relies on a measured size distribution of the contrast agent and well-established properties of the renal and cardiovascular systems. The model fits well (R<sup>2</sup> = 0.9910) with experimental data from samples taken from ten minutes to two weeks after start of infusion. These results support that the cut-off diameter for human renal filtration is 5.5 nm. The agreement between experiment and model implies that there is little or no plasma protein binding to the nanoparticles.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1549963424000431/pdfft?md5=8601ad682c68920fc5432c9e86ab6def&pid=1-s2.0-S1549963424000431-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Size-dependent renal filtration model explains human pharmacokinetics of a functional nanoparticle: The SPAGOPIX-01 clinical trial\",\"authors\":\"\",\"doi\":\"10.1016/j.nano.2024.102774\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>The pharmacokinetics in patients dosed with the nanoparticle-based MRI contrast agent SN132D is explained by a size dependent clearance mechanism and this behavior was modeled numerically. Blood samples from 14 patients were analyzed for silicon (a component of the nanoparticle) by ICP-OES. The pharmacokinetic model has only one free parameter and relies on a measured size distribution of the contrast agent and well-established properties of the renal and cardiovascular systems. The model fits well (R<sup>2</sup> = 0.9910) with experimental data from samples taken from ten minutes to two weeks after start of infusion. These results support that the cut-off diameter for human renal filtration is 5.5 nm. The agreement between experiment and model implies that there is little or no plasma protein binding to the nanoparticles.</p></div>\",\"PeriodicalId\":19050,\"journal\":{\"name\":\"Nanomedicine : nanotechnology, biology, and medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2024-07-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S1549963424000431/pdfft?md5=8601ad682c68920fc5432c9e86ab6def&pid=1-s2.0-S1549963424000431-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nanomedicine : nanotechnology, biology, and medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1549963424000431\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nanomedicine : nanotechnology, biology, and medicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1549963424000431","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Size-dependent renal filtration model explains human pharmacokinetics of a functional nanoparticle: The SPAGOPIX-01 clinical trial
The pharmacokinetics in patients dosed with the nanoparticle-based MRI contrast agent SN132D is explained by a size dependent clearance mechanism and this behavior was modeled numerically. Blood samples from 14 patients were analyzed for silicon (a component of the nanoparticle) by ICP-OES. The pharmacokinetic model has only one free parameter and relies on a measured size distribution of the contrast agent and well-established properties of the renal and cardiovascular systems. The model fits well (R2 = 0.9910) with experimental data from samples taken from ten minutes to two weeks after start of infusion. These results support that the cut-off diameter for human renal filtration is 5.5 nm. The agreement between experiment and model implies that there is little or no plasma protein binding to the nanoparticles.
期刊介绍:
The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine.
Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.