Low renal toxicity of lipoplatin compared to cisplatin in animals

Anticancer Res. 2004 Jul-Aug;24(4):2193-200.

Abstract

Cisplatin is one of the most widely used and effective chemotherapeutic agents for the treatment of several human malignancies. Although the effectiveness of cisplatin is high, its toxicities justify the demand for improved formulations of this drug. A liposomal formulation of cisplatin, Lipoplatin, was developed in order to reduce the systemic toxicity of cisplatin. Mice and rats injected with cisplatin developed renal insufficiency with clear evidence of tubular damage, but those injected with the same dose of Lipoplatin were almost completely free of kidney injury. The maximum levels of total platinum in rat kidneys after intraperitoneal bolus injection of cisplatin or Lipoplatin at similar doses were similar, but the steady state accumulation of total platinum in the kidney was 5 times higher for cisplatin compared to Lipoplatin. This is proposed as one mechanism to explain the low renal toxicity of Lipoplatin.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / toxicity*
  • Cisplatin / administration & dosage
  • Cisplatin / pharmacokinetics
  • Cisplatin / toxicity*
  • Drug Carriers
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / metabolism
  • Liposomes
  • Male
  • Mice
  • Rats

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Liposomes
  • lipoplatin
  • Cisplatin