Sustained-release methotrexate for intracavitary chemotherapy.
Methotrexate was encapsulated into a lipid-based drug-delivery system to create a slow-release formulation (Depo/methotrexate) for intracavitary administration. Depo/methotrexate was stable in storage at 4 degrees C for > 4 months. In human plasma at 37 degrees C, the half-life of drug release was 40 days. After intraperitoneal injection of Depo/methotrexate in mice, the intraperitoneal apparent half-life of free methotrexate was 39.6 h, in contrast to a half-life of 0.5 h for the unencapsulated standard methotrexate (std/methotrexate). In L1210 murine leukemia model, the potency of a single dose of Depo/methotrexate was 334-fold higher, the increased life-span (ILS) was 2-fold greater, and the therapeutic index was 2-fold higher than a single dose of std/methotrexate.
Chatelut
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University of California San Diego, Cancer Center, La Jolla 92093-0812.
Suh
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Kim
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D000818:Animals; D017690:Cell Transplantation; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D007274:Injections, Intraperitoneal; D007939:Leukemia L1210 / Q000188:drug therapy; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation
D003692:Delayed-Action Preparations; D008727:Methotrexate