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KMID : 0811720170210010045
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Korean Journal of Physiology & Pharmacology
2017 Volume.21 No. 1 p.45 ~ p.54
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Metabolism and excretion of novel pulmonary-targeting docetaxel liposome in rabbits
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Wang Jie
Zhang Li
Wang Lijuan
Liu Zhonghong
Yu Yu
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Abstract
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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 ultra-performance 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 Mun 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 Mun may further suggest an alternative species-specific metabolic pathway.
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KEYWORD
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Animal model, Chemotherapy, Cumulative excretion rate, Liquid chromatography, Lung cancer, Mass spectrometry
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