Effect of different quantities of carboxymethyl chitosan modification to pharmacokinetic performance of paclitaxel liposome in rats / 中国临床药理学与治疗学

AIM:To study the effect of different quantities of carboxymethyl chitosan(CMCT) modification to the pharmacokinetic performance of PTX-LP in 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-LP and(0.2)%CMCT modified PTX-LP in rats.Plasma samples were analyzed on a C_(18) 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-LP and(0.2)% CMCT modified PTX-LP follow bi-exponential disposition.T_(1/2?) 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-LP in rats by comparison with unmodified LP.T_(1/2?) and 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.