The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Metabolism and excretion of novel pulmonary-targeting docetaxel liposome in rabbits

  • Wang, Jie (Pharmacy College, Chongqing Medical University) ;
  • Zhang, Li (Pharmacy College, Chongqing Medical University) ;
  • Wang, Lijuan (Pharmacy College, Chongqing Medical University) ;
  • Liu, Zhonghong (Pharmacy College, Chongqing Medical University) ;
  • Yu, Yu (Pharmacy College, Chongqing Medical University)
  • Received : 2016.06.26
  • Accepted : 2016.09.06
  • Published : 2017.01.01
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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 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 $M_{un}$ 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.

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References

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