Pharmacokinetics Of Liposomal Vincristinein Rats And Its Effects On Pharmacodynamics And Toxicity

Purpose: The present study was designed to investigate the pharmacokinetics and biodistribution of liposomal and unencapsulated vincristine in rats bearing walker256 carcinoma following tail-vein injection.Methods: A sensitive and selective high-performance liquid chromatographic (HPLC) method was used to determine the level of vincristine in plasma and tissues. The stable phase was a reversed-phase column (Kromasil?, C18, 250 X 4.6mm) and the mobile phase was composed of methanol-acetonitrile-phosphate buffer (PH=7, 23:52:25, vol. %). The UV detector was set at 220 nm. The flow rate was l.Oml/min, and column temperature was set at 20° C. Vinblastine was used as the internal standard.Results: The pharmacokinetics of both liposomal and nonliposomal vincristine was observed to fit the 2-compartment open model. After a bolus dose of 1 mg/kg, the t1/2 α and t1/2 β is 0.02 hr and 0.30 hr for F-VCR (uncapsulated vincristine) and 2.6 hr and 13.87 hr for L-VCR (liposomal vincristine), respectively. Area under the plasma concentration-time curve (AUC) for F-VCR is relatively small (5.01 mg/L*hr) compared to that of L-VCR (116.82 mg/L*hr). Volume of distribution (Vd) and mean retention time (MRT) for F-VCR is 0.0968 L/kg and 0.36hr, whereas the corresponding values for L-VCR are 0.1694 L/kg and 7.73hr. The levels of vincristine in most tissues are higher when administrated in liposome form except for muscle and brain. The fact that remarkably higher level was detected in tumor when vincristine was given in liposomal form is of great significance. In summary, encapsulation in liposome significantly altered the pharmacokinetic characters of vincristine.