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新型肺靶向多西他赛脂质体在兔体内的代谢与排泄

Metabolism and excretion of novel pulmonary-targeting docetaxel liposome in rabbits.

作者信息

Wang Jie, Zhang Li, Wang Lijuan, Liu Zhonghong, Yu Yu

机构信息

Pharmacy College, Chongqing Medical University, Chongqing 400016, China.

出版信息

Korean J Physiol Pharmacol. 2017 Jan;21(1):45-54. doi: 10.4196/kjpp.2017.21.1.45. Epub 2016 Dec 21.

DOI:10.4196/kjpp.2017.21.1.45
PMID:28066140
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5214910/
Abstract

Our study aims to determine the metabolism and excretion of novel pulmonary-targeting docetaxel liposome (DTX-LP) using the and animal experimental models. The metabolism and excretion of DTX-LP and intravenous DTX (DTX-IN) in New Zealand rabbits were determined with ultraperformance liquid chromatography tandem mass spectrometry. We found DTX-LP and DTX-IN were similarly degraded by liver homogenates and microsomes, but not metabolized by lung homogenates. Ultra-performance liquid chromatography tandem mass spectrometry identified two shared DTX metabolites. The unconfirmed metabolite M differed structurally from all DTX metabolites identified to date. DTX-LP likewise had a similar metabolism to DTX-IN. Conversely, DTX-LP showed significantly diminished excretion in rabbit feces or urine, approximately halving the cumulative excretion rates compared to DTX-IN. Liposomal delivery of DTX did not alter the or drug metabolism. Delayed excretion of pulmonary-targeting DTX-LP may greatly enhance the therapeutic efficacy and reduce the systemic toxicity in the chemotherapy of non-small cell lung cancer. The identification of M may further suggest an alternative species-specific metabolic pathway.

摘要

我们的研究旨在使用[具体动物]和[具体动物]实验模型来确定新型肺靶向多西他赛脂质体（DTX-LP）的代谢和排泄情况。采用超高效液相色谱串联质谱法测定了新西兰兔体内DTX-LP和静脉注射多西他赛（DTX-IN）的代谢和排泄情况。我们发现DTX-LP和DTX-IN在肝脏匀浆和微粒体中的降解情况相似，但在肺匀浆中不会发生代谢。超高效液相色谱串联质谱法鉴定出了两种共同的多西他赛代谢物。未确认的代谢物M在结构上与迄今鉴定出的所有多西他赛代谢物均不同。DTX-LP的代谢情况同样与DTX-IN相似。相反，DTX-LP在兔粪便或尿液中的排泄量显著减少，与DTX-IN相比，累积排泄率约减半。多西他赛的脂质体递送并未改变[具体内容]或[具体内容]药物代谢。肺靶向DTX-LP排泄延迟可能会大大提高非小细胞肺癌化疗的疗效并降低全身毒性。代谢物M的鉴定可能进一步提示了一种物种特异性的替代代谢途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c2f/5214910/4d6152feeb30/kjpp-21-45-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c2f/5214910/80542979fc89/kjpp-21-45-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c2f/5214910/9d6eb990337d/kjpp-21-45-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c2f/5214910/07a4a76035f2/kjpp-21-45-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c2f/5214910/336167c8f71f/kjpp-21-45-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c2f/5214910/c60b6302a979/kjpp-21-45-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c2f/5214910/4d6152feeb30/kjpp-21-45-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c2f/5214910/80542979fc89/kjpp-21-45-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c2f/5214910/9d6eb990337d/kjpp-21-45-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c2f/5214910/07a4a76035f2/kjpp-21-45-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c2f/5214910/336167c8f71f/kjpp-21-45-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c2f/5214910/c60b6302a979/kjpp-21-45-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c2f/5214910/4d6152feeb30/kjpp-21-45-g006.jpg

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