A comparison of pharmacokinetics between paclitaxel liposome for injection and commercial paclitaxel injection in patients with cancer

Objective: To establish a liquid chromatography-mass spectometry (LC-MS) method for determination of paclitaxel in human plasma, and to study the pharmacokinetics of paclitaxel liposome for injection (L-PTX) and conventional paclitaxel injection (C-PTX) in patients with cancer. Methods: An open, randomized and controlled study was designed. Sixteen patients with cancer were divided into two groups receiving a single dose of 175 mg/m2 L-PTX and C-PTX, respectively. The blood samples were collected at 1.5 and 3 h during intravenous infusion and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 and 72 h after the end of infusion. The drug concentration in the blood was determined by LC-MS method, and the pharmacokinetic parameters were calculated by DAS2.0 software and compared. Results: The main pharmacokinetic parameters of L-PTX and C-PTX after a single intravenous infusion of 175 mg/m2 were as follows: peak plasma concentrations (Cmax) were 6 455 ± 2 247 µg/L and 7 400 ± 1 542 µg/L; the areas under the plasma concentration-time curve (AUC0-∞) were 14 812 ± 2 846 µg·h·L-1 and 21 693 ± 2 657 µg·h·L-1; the plasma elimination half-life (t1/2z) were 30.5 ± 7.3 h and 13.7 ± 3.2 h; the apparent volumes of distribution (Vz) were 526.8 ± 112.1 L/m2 and 162.9 ± 49.1 L/m2; the plasma clearance rates (CLz) were 12.3 ± 2.7 L·h-1·m-2 and 8.2 ± 1.0 L·h-1·m-2, respectively. The statistical analysis showed that there was a significant difference in major pharmacokinetic parameters between L-PTX and C-PTX (P＜0.05). Conclusion: The pharmacokinetic properties of paclitaxel in vivo are changed when it is encapsulated by liposome. Compared with C-PTX, the L-PTX is uniquely different in distribution and elimination aspects in patients with cancer, and it demonstrates improved tissue affinity and effect of delayed release. DOI:10.3781/j.issn.1000-7431.2011.12.010