title: Metabolism and excretion of novel pulmonary-targeting docetaxel liposome in rabbits.
abstract: Our study aims to determine the metabolism and excretion of novel pulmonary-targeting docetaxel liposome (DTX-LP) using thein vitroandin vivoanimal 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 degradedin vitroby 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 Mundiffered structurally from all DTX metabolites identified to date. DTX-LP likewise had a similarin vivometabolism 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 thein vitroorin vivodrug 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 Munmay further suggest an alternative species-specific metabolic pathway.
authors.affiliation: Pharmacy College, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Pharmacy College, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Pharmacy College, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Pharmacy College, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Zhonghong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Pharmacy College, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yu
keywords: Animal model; Chemotherapy; Cumulative excretion rate; Liquid chromatography; Lung cancer; Mass spectrometry