Your browser doesn't support javascript.
loading
Montrer: 20 | 50 | 100
Résultats 1 - 1 de 1
Filtre
Ajouter des filtres








Gamme d'année
1.
Biomolecules & Therapeutics ; : 553-558, 2017.
Article Dans Anglais | WPRIM | ID: wpr-107202

Résumé

Paclitaxel (PTX) is one of the most frequently used anticancer agent for treating refractory ovarian cancer, metastatic breast cancer and non-small cell lung cancer. However, its oral administration is impeded by very low bioavailability (<5%) due to the P-glycopprotein (P-gp) efflux pump effect. This study investigated in vitro and in vivo P-gp inhibitory effects of adamantyl derivatives AC-603 and AC-786 in rats. Two adamantyl derivatives tested in this study increased the cytotoxicity of daunomycin (DNM) in P-gp overexpressed cell line by inhibiting P-gp efflux function. Pharmacokinetics of PTX with orally co-administered P-gp inhibitors were assessed in rats to improve PTX absorption. The pharmacokinetic parameters of PTX were determined in rats after intravenous (2 mg/kg) or oral (25 mg/kg) administration in the presence or absence of verapamil (a positive control), AC-603 or AC-786 (0.5 mg/kg or 5 mg/kg). Compared to control group (PTX alone), experimental groups (PTX with AC-603 or AC-786) significantly increased the area under the plasma concentration-time curve of PTX following oral administration by 1.7–2.2 fold. The volume of distribution and total clearance of PTX were decreased, while other parameters were not significantly changed. In conclusion, co-administration of AC-603 or AC-786 enhanced the relative bioavailability of orally administered PTX as compared to control.


Sujets)
Animaux , Rats , Absorption , Administration par voie orale , Biodisponibilité , Tumeurs du sein , Carcinome pulmonaire non à petites cellules , Lignée cellulaire , Daunorubicine , Techniques in vitro , Tumeurs de l'ovaire , Glycoprotéine P , Paclitaxel , Pharmacocinétique , Plasma sanguin , Vérapamil
SÉLECTION CITATIONS
Détails de la recherche