title: Pharmacokinetics and biodistribution of itraconazole in rats and mice following intravenous administration in a novel liposome formulation.
abstract: Novel itraconazole (ITZ)-loaded liposomes (ITZ-LPs) were prepared and their pharmacokinetics and biodistribution were assessed in comparison with commercial formulations (ITZ-CD). The ITZ-LPs were prepared by thin-film hydration method and the physicochemical characterizations of the ITZ-LPs were evaluated. The pharmacokinetics and biodistribution were studied in the rats and mice, and compared with commercially available formulations (Sporanox((R))) after administration by the tail vein at a dose of 10 mg/kg. The concentration of ITZ in plasma and tissues was determined by means of HPLC-MS/MS. The size distribution of the liposomes was 264.5 nm and the entrapment efficiency of ITZ-LPs was 73.82 +/- 0.73%. In pharmacokinetics study, the two formulations demonstrated pronounced differences following i.v. administration to rats. The AUC(0-->24 h) for ITZ-CD was 87.12 mg/L.h and that for ITZ-LPs was 155.47 mg/L.h (p < 0.05). The MRT(0-->24 h) value was 1.70 h for ITZ-CD and 3.68 h for ITZ-LPs. In tissue distribution study, there were no differences of distributions in the lung between two formulations. Nevertheless, in the liver and spleen, itraconazole levels for the group treated with ITZ-LPs were significantly higher than those for the group treated with ITZ-CD. Meanwhile, the low distribution of ITZ-LPs in heart and kidney was of great advantage to reduce the toxicity for heart and kidney. These results indicated that the ITZ-LPs can be a potential intravenous formulation of itraconazole.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Harbin Medical University, Harbin, 150086, China.
authors.forename: Jingling
authors.initials: J
authors.lastname: Tang
authors.forename: Hua
authors.initials: H
authors.lastname: Wei
authors.forename: Hongmei
authors.initials: H
authors.lastname: Liu
authors.forename: Hongyu
authors.initials: H
authors.lastname: Ji
authors.forename: Di
authors.initials: D
authors.lastname: Dong
authors.forename: Daling
authors.initials: D
authors.lastname: Zhu
authors.forename: Linhua
authors.initials: L
authors.lastname: Wu
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical; D007275:Injections, Intravenous; D017964:Itraconazole / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008081:Liposomes; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D014018:Tissue Distribution / Q000502:physiology
chemical_list: D008081:Liposomes; D017964:Itraconazole