A comparison of pharmacokinetics between paclitaxel liposome for injection and commercial paclitaxel injection in patients with cancer
10.3781/j.issn.1000-7431.2011.12.010
- Author:
Jun QIAN
1
Author Information
1. Department of Medical Oncology
- Publication Type:Journal Article
- Keywords:
Liposome;
Liquid chromatography-mass spectometry;
Neoplasms;
Paclitaxel;
Pharmacokinetics
- From:
Tumor
2011;31(12):1103-1107
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To establish a liquid chromatography-mass spectometry (LC-MS) method fordetermination of paclitaxel in human plasma, and to study the pharmacokinetics of paclitaxel liposomefor injection (L-PTX) and conventional paclitaxel injection (C-PTX) in patients with cancer. Methods: Anopen, randomized and controlled study was designed. Sixteen patients with cancer were divided into twogroups receiving a single dose of 175 mg/m2 L-PTX and C-PTX, respectively. The blood samples werecollected 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 hafter the end of infusion. The drug concentration in the blood was determined by LC-MS method, andthe pharmacokinetic parameters were calculated by DAS2.0 software and compared. Results: The mainpharmacokinetic parameters of L-PTX and C-PTX after a single intravenous infusion of 175 mg/m2 wereas follows: peak plasma concentrations (Cmax) were 6 455 ± 2 247 μg/L and 7 400 ± 1 542 μg/L; theareas under the plasma concentration-time curve (AUC0-∞) were 14 812 ± 2 846 μg·h· L-1 and 21 693 ± 2 657 mu;g·h·L-1 the plasma elimination half-life ( t1/2z) were 30.5 ± 7.3 h and 13.7 ± 3.2 h; the apparentvolumes of distribution (Vz) were 526.8 ± 112.1 L/m2 and 162.9 ± 49.1 L/m2; the plasma clearancerates (CLz) were 12.3 ± 2.7 L·h-1·m-2 and 8.2 ± 1.0 L·h-1·m-2, respectively. The statistical analysisshowed 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 itis encapsulated by liposome. Compared with C-PTX, the L-PTX is uniquely different in distribution andelimination aspects in patients with cancer, and it demonstrates improved tissue affinity and effect ofdelayed release. Copyright© 2011 by TUMOR.
