A comparison of pharmacokinetics between paclitaxel emulsion and injection in beagle dogs

Objective:To establish an HPLC-MS/MS method for the determination of paclitaxel(Taxol)in beagle dog plasma,and evaluate and compare the pharmacokinetic characteristics of two formulations of paclitaxel.Methods: The cross-over design(two periods) was employed.Eight beagle dogs were administrated with a single iv.dose of 40 mg paclitaxel emulsion and reference preparation,respectively.The concentration of paclitaxel in plasma at different sampling time was determined by HPLC-MS/MS.The pharmacokinetic parameters were calculated with DAS(2.0.1version) program and compared by statistic analysis.Results: The mean concentration-time curves of both paclitaxel emulsion and reference preparation were fitted to two-compartment model with the main pharmacokinetic parameters as follows: t1/2z were(5.07±1.30) and(4.62±0.976)h;Clz were(15.1±2.43) and(10.1±2.35) h·L-1;Vz were(111±38.8) and(65.8±16.4)L;Cmax were(1 416±162)and(2 231±519)μg·L-1;AUC0-680min were(2 442±535) and(3 753±771)μg·h·L-1;AUC0-∞ were(2 725±559)and(4 163±922)μg·h·L-1.Conclusion: The pharmacokinetic parameters AUC,Clz,Vz and Cmax of the two preparations were significantly different(P0.05,paired t-test).The AUC ratio of paclitaxel emulsion and reference preparation was(0.665±0.146).