Yi Yilwoong, Yoon Hye Jeong, Kim Bong Oh, Shim Myungseob, Kim Sun-Ok, Hwang Sung-Joo, Seo Min Hyo
Samyang Pharmaceuticals R&D Center, Yuseong-Gu, Daejeon 305-717, South Korea.
J Control Release. 2007 Jan 22;117(1):59-67. doi: 10.1016/j.jconrel.2006.10.001. Epub 2006 Oct 6.
A mixed polymeric micelle formulation of itraconazole (ITZ-PM) was prepared using monomethoxy poly(ethylene glycol)-b-poly(lactic acid) and poly(lactic acid) as drug carrier materials. The ITZ-PM formulation remarkably increased the itraconazole solubility up to 15 mg/mL in aqueous media and provided stable solutions at a wide range of concentrations and pH's. In toxicity studies of single and 28-day repeated administrations to rats and dogs, ITZ-PM was well tolerated at dose levels corresponding to clinical doses. The pharmacokinetic profiles of ITZ-PM for itraconazole and its major metabolite, hydroxy-itraconazole, were comparable to those of the cyclodextrin formulations (Sporanox(R) Injection and Oral Solution) in rats and dogs. These results suggest that ITZ-PM can be an advantageous formulation for both intravenous and oral routes.
以单甲氧基聚（乙二醇）-b-聚（乳酸）和聚（乳酸）作为药物载体材料，制备了伊曲康唑混合聚合物胶束制剂（ITZ-PM）。ITZ-PM制剂在水性介质中显著提高了伊曲康唑的溶解度，可达15mg/mL，并在广泛的浓度和pH值范围内提供稳定的溶液。在对大鼠和犬进行单次及28天重复给药的毒性研究中，ITZ-PM在相当于临床剂量的剂量水平下耐受性良好。ITZ-PM中伊曲康唑及其主要代谢产物羟基伊曲康唑的药代动力学特征与大鼠和犬体内环糊精制剂（斯皮仁诺®注射剂和口服溶液）的药代动力学特征相当。这些结果表明，ITZ-PM对于静脉内和口服给药途径而言可能是一种有利的制剂。
