title: A mixed polymeric micellar formulation of itraconazole: Characteristics, toxicity and pharmacokinetics.
abstract: 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.
authors.affiliation: Samyang Pharmaceuticals R&D Center, Yuseong-Gu, Daejeon 305-717, South Korea.
authors.forename: Yilwoong
authors.initials: Y
authors.lastname: Yi
authors.forename: Hye Jeong
authors.initials: HJ
authors.lastname: Yoon
authors.forename: Bong Oh
authors.initials: BO
authors.lastname: Kim
authors.forename: Myungseob
authors.initials: M
authors.lastname: Shim
authors.forename: Sun-Ok
authors.initials: SO
authors.lastname: Kim
authors.forename: Sung-Joo
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Min Hyo
authors.initials: MH
authors.lastname: Seo
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D019540:Area Under Curve; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D004285:Dogs; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D017964:Itraconazole / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D019344:Lactic Acid; D007928:Lethal Dose 50; D008297:Male; D008823:Micelles; D010316:Particle Size; D011091:Polyesters; D011092:Polyethylene Glycols; D011098:Polyglactin 910; D011108:Polymers; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000935:Antifungal Agents; D008823:Micelles; D011091:Polyesters; D011108:Polymers; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D017964:Itraconazole; D019344:Lactic Acid; D011098:Polyglactin 910; D011092:Polyethylene Glycols; C033616:poly(lactide)