Low renal toxicity of lipoplatin compared to cisplatin in animals.
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.
Devarajan
Prasad
P
Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA. prasad.devarajan@cchmc.org
Tarabishi
Ridwan
R
Mishra
Jaya
J
Ma
Qing
Q
Kourvetaris
Andreas
A
Vougiouka
Maria
M
Boulikas
Teni
T
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D004337:Drug Carriers; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism; D008081:Liposomes; D008297:Male; D051379:Mice; D051381:Rats
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; C503131:lipoplatin; D002945:Cisplatin