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Int J Pharm ; 399(1-2): 116-20, 2010 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-20727390

RESUMEN

As with many other anti-cancer agents, docetaxel is a substrate for ATP-binding cassette transporters such as P-glycoprotein and its metabolism is mainly catalysed by CYP3A. In order to improve the oral bioavailability of docetaxel, a component of turmeric, curcumin, which can down-regulate the intestinal P-glycoprotein and CYP3A protein levels, was used for the pre-treatment of rats before the oral administration of docetaxel. Curcumin (100 mg/kg) did not significantly modify the pharmacokinetics of docetaxel when given orally 30 min before the administration of docetaxel. However, the C(max) of docetaxel in rats pre-treated with curcumin for four consecutive days was significantly increased (p<0.01) by about 10 times compared to that of the docetaxel control, and the area under the plasma concentration-time curve (AUC) was about eight times higher than that of the control. Consequently, the absolute bioavailability of docetaxel in the treatment group (four days of curcumin at 100 mg/kg) was about 40%, which was a significant increase of about eightfold in comparison to the control value. Thus, the oral bioavailability of docetaxel was enhanced by the co-administration of regular curcumin. It could be possible to administer docetaxel orally, besides the established i.v. route.


Asunto(s)
Antineoplásicos/farmacocinética , Curcumina/uso terapéutico , Inhibidores del Citocromo P-450 CYP3A , Inhibidores Enzimáticos/uso terapéutico , Taxoides/farmacocinética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Administración Oral , Animales , Antineoplásicos/sangre , Antineoplásicos/farmacología , Disponibilidad Biológica , Cromatografía Líquida de Alta Presión , Curcumina/farmacología , Docetaxel , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Inyecciones Intravenosas , Masculino , Ratas , Ratas Sprague-Dawley , Especificidad por Sustrato , Taxoides/sangre , Taxoides/farmacología
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