title: Pharmacokinetics of liposomal-encapsulated and un-encapsulated vincristine after injection of liposomal vincristine sulfate in beagle dogs.
abstract: OBJECTIVE
  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. C2 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.
authors.affiliation: Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhong
authors.forename: Wenxue
authors.initials: W
authors.lastname: Mao
authors.forename: Rong
authors.initials: R
authors.lastname: Shi
authors.forename: Peng
authors.initials: P
authors.lastname: Jiang
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Rong
authors.initials: R
authors.lastname: Zhu
authors.forename: Tianming
authors.initials: T
authors.lastname: Wang
authors.forename: Yueming
authors.initials: Y
authors.lastname: Ma
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D007275:Injections, Intravenous; D008081:Liposomes / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D011897:Random Allocation; D052616:Solid Phase Extraction; D053719:Tandem Mass Spectrometry / Q000379:methods; D014750:Vincristine / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D014750:Vincristine