Original Article

Pharmacokinetic characteristics of vincristine sulfate liposomes in patients with advanced solid tumors

Zhao Yan, Zhong-ling Zhu, Zheng-zi Qian, Ge Hu, Hua-qing Wang, Wan-hui Liu, Guang Cheng
DOI: 10.1038/aps.2012.44


Aim: To evaluate the single- and multiple-dose pharmacokinetics of vincristine sulfate liposomes (VSLI) in patients with advanced solid tumors.
Methods: In single-dose pharmacokinetic study, 16 patients were administered VSLI (1.5, 2.0, or 2.3 mg·m−2) through intravenous infusion. Another 6 patients receiving vincristine sulfate (VCR, 2.0 mg) were taken as the control. In multiple-dose pharmacokinetic study, 12 patients were administered VSLI (1.5 or 1.8 mg·m−2) through intravenous infusion weekly for 4 consecutive weeks. The plasma concentration of VSLI was determined using the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method.
Results: After intravenous infusion of the single dose of VSLI, the plasma concentrations were characterized by bi-exponential decline curves. No statistically significant differences were observed between the main pharmacokinetic parameters in the 3 dose groups. Compared with the patients receiving VCR, the patients treated with VSLI displayed an increase in the area under the plasma concentration vs time curve (AUC), and a decrease in plasma clearance rates. On the 4th cycle in the multiple-dose study, the plasma concentration of VCR in all subjects prior to the weekly administration was below the lower limit of quantification (LLOQ). The calculated pharmacokinetic parameters from the subjects in the multiple- and single-dose (1.5 mg·m−2) groups had no significant differences. Although the administration of liposomal VCR may significantly elevate the plasma concentration of VCR, VSLI-associated adverse events were similar to those associated with conventional VCR.
Conclusion: VSLI exhibits a lower clearance and a higher AUC compared with conventional VCR. No accumulation was observed in patients exposed to VSLI for 4 consecutive weeks. VSLI was generally tolerated in the subjects. The phase II dose of VSLI may be recommended as 4 doses of 1.5 mg·m−2 for treatment of patients with advanced solid tumors.

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