T-13 and T-26, the novel taxanes with improved oral bioavailability in rats.
Sci Rep
; 10(1): 3211, 2020 02 21.
Article
en En
| MEDLINE
| ID: mdl-32081942
ABSTRACT
In an attempt to improve the oral bioavailability of taxanes, a series of new analogues were synthesized and tested in a panel of human tumor cell lines and cellular permeability assays. Compounds T-13 and T-26 showed potent cytotoxicity and exhibited the highest permeability, so they were selected for pharmacokinetic studies. Here, pharmacokinetics of T-13 and T-26 were studied after intravenous injection (5 mg/kg) and oral administration (60 mg/kg) in male Sprague-Dawley (S.D.) rats, respectively. Plasma concentrations were characterized using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The oral bioavailability of T-13 and T-26 was determined to be 10.71% and 65.79%, respectively. Compounds T-13 and T-26 were both poor substrates of P-glycoprotein (P-gp), and they had a much higher bioavailability than paclitaxel, especially T-26. T-26 with good oral bioavailability represented a potential candidate for potent antitumor activity given oral administration.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Disponibilidad Biológica
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Diseño de Fármacos
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Taxoides
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Sci Rep
Año:
2020
Tipo del documento:
Article