title: Prolonged blood concentration of prednisolone after intravenous injection of liposomal palmitoyl prednisolone.
abstract: We compared the pharmacokinetic behavior of drugs after an intravenous administration of prednisolone (PLS), palmitoyl prednisolone (Pal-PLS), and liposomal Pal-PLS in rats. Pal-PLS showed higher lipophilicity and higher binding to plasma protein than PLS, and PLS regeneration in rat blood and liver homogenates. After the intravenous administration of Pal-PLS solution in polyethylene glycol (PEG) 400 to rats, Pal-PLS disappeared from the blood in a two-phase mode and PLS was rapidly regenerated. Pal-PLS showed a significantly higher accumulation than PLS in the liver and lung. The administration of Pal-PLS incorporated into egg yolk phosphatidylcholine (EggPC)/cholesterol (Chol) liposomes enhanced Pal-PLS concentrations in the blood, liver, and lung compared to that of Pal-PLS solution in PEG 400, suggesting the rapid removal of liposomes by the mononuclear phagocytic system. Pal-PLS incorporated into PEGylated liposomes constituted with EggPC/Chol/1% L-alpha-distearoylphosphatidylethanolamine (DSPE)-PEG 2000 and EggPC/Chol/10% DSPE-PEG 2000 decreased the initial distribution of Pal-PLS, and successfully maintained the blood concentrations of Pal-PLS and PLS. Thus, we could change the pharmacokinetics of PLS by introducing the palmitoyl function into the molecule and its liposomal formulation including PEGylation. This is the first study to evaluate liposomal PLS constituted with a lipophilic derivative and PEG lipids.
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital of Medicine and Dentistry, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Mugen
authors.initials: M
authors.lastname: Teshima
authors.forename: Shintaro
authors.initials: S
authors.lastname: Fumoto
authors.forename: Koyo
authors.initials: K
authors.lastname: Nishida
authors.forename: Junzo
authors.initials: J
authors.lastname: Nakamura
authors.forename: Kaname
authors.initials: K
authors.lastname: Ohyama
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ichikawa
authors.forename: Mikiro
authors.initials: M
authors.lastname: Nakashima
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D007275:Injections, Intravenous; D008081:Liposomes; D008297:Male; D009928:Organ Specificity / Q000187:drug effects / Q000502:physiology; D011239:Prednisolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008081:Liposomes; C500349:palmitoyl prednisolone; D011239:Prednisolone