title: Comparative pharmacokinetics of free muramyl tripeptide phosphatidyl ethanolamine (MTP-PE) and liposomal MTP-PE.
abstract: The comparative pharmacokinetics of free MTP-PE (muramyl tripeptide phosphatidyl ethanolamine) and MTP-PE entrapped in negatively charged multilamellar liposomes (liposomal MPT-PE) was evaluated in rats at a bolus intravenous (i.v.) dose of 0.2 mg/kg and in dogs at a bolus i.v. dose of 0.1 mg/kg. Additional studies were performed with the free form in rats (1.4 mg/kg, bolus i.v.) and dogs (1 mg/kg, bolus i.v.) and with the liposomal form in dogs (0.5 mg/kg, bolus i.v.). Plasma samples were obtained at various times up to 48 h postinjection and assayed for the drug by a chemiluminescence immunoassay. The pharmacokinetic data regarding liposomal MTP-PE describe the distribution of free drug released from liposomes and total drug concentrations. The present studies demonstrate that the distribution characteristics of MTP-PE changed dramatically depending on the dosage form. The elimination kinetics of free MTP-PE from blood is substantially slower than that of the liposomal drug. For liposomal MTP-PE, free drug levels in plasma are very low compared with free MTP-PE. In rats at a dose of 0.2 mg/kg, 96% of MTP-PE contained in liposomes is removed from the plasma compartment 10 min after injection, and in dogs at a dose of 0.1 mg/kg, 100% of MTP-PE contained in liposomes is removed in the same time period. This rapid phase of liposome clearance is followed by a slower rate of clearance for the remainder of the liposomes in rats at a dose of 0.2 mg/kg and in dogs at a dose of 0.5 mg/kg.
authors.affiliation: Ciba-Geigy Limited, Oncology and Virology Department, Basel, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Gay
authors.forename: J M
authors.initials: JM
authors.lastname: Cardot
authors.forename: C
authors.initials: C
authors.lastname: Schnell
authors.forename: P
authors.initials: P
authors.lastname: van Hoogevest
authors.forename: D
authors.initials: D
authors.lastname: Gygax
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D004285:Dogs; D004337:Drug Carriers; D008081:Liposomes; D008297:Male; D010714:Phosphatidylethanolamines / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D010714:Phosphatidylethanolamines; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine