Pharmacokinetics and tissue distribution of iv injection of polyphase liposome-encapsulated cisplatin (KM-1) in rats

Acta Pharmacol Sin. 2003 Jun;24(6):589-92.

Abstract

Aim: The pharmacokinetics and biodistribution of cisplatin encapsulated in polyphase liposome (KM-1) were compared with those of free drug in rats.

Methods: The platinum levels in serum and normal organs, after a single dose of iv injection of free or encapsulated cisplatin to rats, were determined by induced coupled plasma atomic emission spectrometry.

Results: Serum platinum concentration-time curve after a single iv dose of KM-1 4.5 mg/kg in rats was fitted with an open three-compartment model. The pharmacokinetic parameters were as follows: Vc=0.10 L/kg, T1/2pai=0.3 h, T1/2alpha=3.5 h, T1/2beta=2.7 h, AUC=265 mg.h.L(-1), and CL(s) =0.02 g.L.h(-1). KM-1 was cleared from the circulation much more slowly than free cisplatin. Liver and spleen had the highest concentration of platinum after KM-1 treatment.

Conclusion: KM-1 remained in the bloodstream longer than its free drug, and was taken mainly by the reticuloendothelial system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics*
  • Cisplatin / administration & dosage
  • Cisplatin / pharmacokinetics*
  • Drug Carriers
  • Injections, Intravenous
  • Liposomes
  • Liver / metabolism
  • Male
  • Platinum / analysis
  • Platinum / blood
  • Rats
  • Rats, Wistar
  • Spleen / metabolism
  • Tissue Distribution

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Liposomes
  • Platinum
  • Cisplatin