Metabolism and excretion of novel pulmonary-targeting docetaxel liposome in rabbits
Metabolism and excretion of novel pulmonary-targeting docetaxel liposome in rabbits
- 대한생리학회-대한약리학회
- The Korean Journal of Physiology & Pharmacology
- 제21권 제1호
- : SCOPUS, SCIE, KCI등재
- 2017.01
- 45 - 54 (10 pages)
Our study aims to determine the metabolism and excretion of novel pulmonary-targeting docetaxel liposome (DTX-LP) using the <i>in vitro</i> and <i>in vivo</i> 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<i> in vitro</i> 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<sub>un</sub> differed structurally from all DTX metabolites identified to date. DTX-LP likewise had a similar <i>in vivo</i> 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<i> in vitro</i> or <i>in vivo</i> 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<sub>un</sub> may further suggest an alternative species-specific metabolic pathway.