Pharmacokinetics and biodistribution of itraconazole in rats and mice following intravenous administration in a novel liposome formulation

• Published in: Drug delivery Vol. 17; no. 4; pp. 223 - 230
• Main Authors: Tang, Jingling, Wei, Hua, Liu, Hongmei, Ji, Hongyu, Dong, Di, Zhu, Daling, Wu, Linhua
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 01.05.2010; Taylor & Francis
• Subjects: Animals; Chemistry, Pharmaceutical; Injections, Intravenous; Itraconazole; Itraconazole - administration & dosage; Itraconazole - pharmacokinetics; Liposomes; Male; Mice; pharmacokinetics; Rats; Rats, Wistar; Species Specificity; tissue distribution; Tissue Distribution - physiology
• ISSN: 1071-7544; 1521-0464
• DOI: 10.3109/10717541003667822

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®) 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 AUC0→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 MRT0→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.