Abstract: AIM: To study the effect of different quantities of carboxymethyl chitosan (CMCT)modification to the pharmacokinetic performance of PTX-LPin rats.METHODS: Plasma was extracted with tert-butyl methyl ether and Norethisterone was employed as internal standard after i.v.unmodified PTX-LP,0.1%CMCT modified PTX-LPand 0.2%CMCT modified PTX-LPin rats.Plasma samples were analyzed on a C18 column at 227 nm and the mobile phase was methanol and water (65∶35,v/v).RESULTS: The plasma concentration-time profile in rats after iv.unmodified PTX-LP,0.1%CMCT modified PTX-LPand 0.2% CMCT modified PTX-LPfollow bi-exponential disposition.T_1/2β are 11.20,15.55 and 30.6 h respectively,AUC were 2541.99,2748.78 and 3451.64 mg·L^-1·min for each of them.CONCLUSION: Significant changes of in vivo pharmacokinetic performance have been found after CMCT modification to PTX-LPin rats by comparison with unmodified LP.T_1/2βand circulation time in plasma have been lengthened and AUC has been improved in some extent.We found that this kind of long circulating action had some correlation with the quantities of CMCT employed.

Key words: paclitaxel, liposome, carboxymethyl chitosan, long circulating action, pharmacokinetics