Pharmacokinetics of liver-targeted docetaxel liposomes modified with 6-O-acyl-D-galactose esters in rabbits.

The purpose of the present study was to investigate the pharmacokinetics of docetaxel liposomes modified with 6-O-acyl-D-galactose esters (Gal-DOC-L) in rabbits. A simple, rapid and sensitive high-performance liquid chromatography (HPLC) method was developed for the determination of docetaxel. Gal-DOC-L was intravenously administered to rabbits with norethisterone as the internal standard and the blood samples were collected from ear marginal veins at 0.083, 0.25, 0.5, l, 2, 4, 6, 8, 12, 16 and 24 h after treatment. The plasma concentration of docetaxel was determined by HPLC and the pharmacokinetic parameters were calculated. Docetaxel injection (DOC-I) was studied simultaneously. The results showed that the area under the curve(0-∞), t1/2α and t1/2β of Gal-DOC-L was significantly higher, while the total body clearance was lower than that of DOC-I. The results indicated that Gal-DOC-L was able to maintain a relatively high blood concentration in vivo and prolong the treatment time.