Metabolism and excretion of novel pulmonary-targeting docetaxel liposome in rabbits.
10.4196/kjpp.2017.21.1.45
- Author:
Jie WANG
1
;
Li ZHANG
;
Lijuan WANG
;
Zhonghong LIU
;
Yu YU
Author Information
1. Pharmacy College, Chongqing Medical University, Chongqing 400016, China. Yuyu_CQMU@outlook.com
- Publication Type:Original Article
- Keywords:
Animal model;
Chemotherapy;
Cumulative excretion rate;
Liquid chromatography;
Lung cancer;
Mass spectrometry
- MeSH:
Animal Experimentation;
Carcinoma, Non-Small-Cell Lung;
Chromatography, Liquid;
Drug Therapy;
Feces;
In Vitro Techniques;
Liposomes*;
Liver;
Lung;
Lung Neoplasms;
Mass Spectrometry;
Metabolic Networks and Pathways;
Metabolism*;
Microsomes;
Models, Animal;
Rabbits*;
Tandem Mass Spectrometry
- From:The Korean Journal of Physiology and Pharmacology
2017;21(1):45-54
- CountryRepublic of Korea
- Language:English
-
Abstract:
Our study aims to determine the metabolism and excretion of novel pulmonary-targeting docetaxel liposome (DTX-LP) using the in vitro and in vivo 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 in vitro 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(un) differed structurally from all DTX metabolites identified to date. DTX-LP likewise had a similar in vivo 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 in vitro or in vivo 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(un) may further suggest an alternative species-specific metabolic pathway.
