Modulation of the peritoneal clearance of liposomal cytosine arabinoside by blank liposomes.
Liposomes containing cytosine arabinoside (ara-C) release drug slowly and can be used to maintain a locally high concentration of ara-C in the peritoneal cavity for intracavitary chemotherapy. However, a significant amount of active drug does reach the systemic circulation and contributes to systemic toxicity. We have devised a novel method of decreasing toxicity and increasing intraperitoneal half-life by pretreatment with "blank" liposomes containing no active drug. This technique has resulted in prolongation of intraperitoneal half-life of the liposomal ara-C from 21 h to 165 h, enabling maintenance of a therapeutic drug concentration even at 11 days after initial injection. One hundred percent cures (60-day survival) were achieved with a single-dose therapy begun 1 day after i.p. implantation of 10(6) L1210 leukemia cells.
D000818:Animals; D003561:Cytarabine / Q000378:metabolism*; D007700:Kinetics; D008081:Liposomes / Q000008:administration & dosage* / Q000378:metabolism; D051379:Mice; D010529:Peritoneal Cavity / Q000378:metabolism*
D008081:Liposomes; D003561:Cytarabine