Metabolism and excretion of novel pulmonary-targeting docetaxel liposome in rabbits
The Korean Journal of Physiology and Pharmacology
; : 45-54, 2017.
Article
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| ID: wpr-728258
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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 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.
Texte intégral:
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Indice:
WPRIM
Sujet Principal:
Spectrométrie de masse
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Techniques in vitro
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Chromatographie en phase liquide
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Carcinome pulmonaire non à petites cellules
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Modèles animaux
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Expérimentation animale
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Traitement médicamenteux
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Spectrométrie de masse en tandem
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Voies et réseaux métaboliques
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Fèces
Limites du sujet:
Animals
langue:
En
Texte intégral:
The Korean Journal of Physiology and Pharmacology
Année:
2017
Type:
Article