Pharmacokinetics of liposomal-encapsulated and un-encapsulated vincristine after injection of liposomal vincristine sulfate in beagle dogs

Purpose

Vincristine sulfate (VCR) is a potent and widely used anti-tumor drug. Encapsulating VCR with liposomes improves its therapeutic index. However, there is little known about the pharmacokinetic features of un-encapsulated VCR (UE-VCR) and encapsulated VCR (E-VCR).

Methods

Two groups of beagle dogs were intravenously administered a single 0.07 mg/kg dose of VCR liposomal injection (L-VCR) and VCR ordinary injection (I-VCR), respectively. The concentrations of UE-VCR, E-VCR and total VCR (T-VCR) were determined by separating UE-VCR and E-VCR, using solid-phase extraction and validated liquid chromatography-tandem mass spectrometry-based methods. Pharmacokinetic parameters were calculated, using the compartment model. The pharmacokinetic parameters of L-VCR and I-VCR were compared using a Student’s t test.

Results

After intravenous injection of L-VCR, the pharmacokinetic parameters of E-VCR were similar to those of T-VCR. The concentrations of UE-VCR were very low, and its AUC _0–72h was only 2.5 % that of T-VCR. Compared with I-VCR, plasma AUC of E-VCR increased, with significantly extended distribution t _1/2 and reduced distribution volume of the peripheral department. C_2 min and AUC _0–1h of plasma UE-VCR decreased, with a similar elimination t _1/2.

Conclusions

The increased therapeutic index of L-VCR is demonstrated by the pharmacokinetic features, higher exposure to E-VCR and lower peak concentration of UE-VCR, following intravenous injection.