title: Hydroxy-itraconazole pharmacokinetics is similar to that of itraconazole in immunocompromised patients receiving oral solution of itraconazole.
abstract: BACKGROUND
  The pharmacokinetic variability of hydroxy-itraconazole (OH-ITZ), an active metabolite of itraconazole (ITZ), is not fully known.
  
  
  METHODS
  Oral solution of ITZ was administered in 46 immunocompromised patients as a single 200 mg dose for at least 12 days. The plasma concentrations of ITZ, active OH-ITZ, and keto-itraconazole (keto-ITZ), an inactive metabolite, 12 h after administration were determined by LC-UV or LC-MS/MS.
  
  
  RESULTS
  The mean±SD of plasma concentrations of ITZ, OH-ITZ, and keto-ITZ were 833±468, 798±454, and 3.94±2.68 μg/l, respectively. A greater correlation coefficient was observed between plasma concentrations of ITZ and OH-ITZ (r=0.90, P<0.01) than between OH-ITZ and keto-ITZ (r=0.44, P<0.01). Plasma concentration of OH-ITZ was inversely correlated with concentration ratio of keto-ITZ to OH-ITZ (r=-0.52, P<0.01). Plasma concentrations of ITZ and OH-ITZ were correlated with serum concentration of albumin (r=0.36, P=0.01 and r=0.37, P=0.01) and estimated glomerular filtration rate (r=-0.27, P=0.08 and r=-0.35, P=0.02).
  
  
  CONCLUSIONS
  The pharmacokinetic variability of OH-ITZ was associated with saturated metabolism to keto-ITZ, serum concentration of albumin, and renal function in immunocompromised patients. The plasma concentration of OH-ITZ was strongly correlated with that of ITZ. Prevention of fungal infections can be improved by determining the plasma concentration of ITZ or OH-ITZ.
authors.affiliation: Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Mino
authors.forename: Takafumi
authors.initials: T
authors.lastname: Naito
authors.forename: Takayuki
authors.initials: T
authors.lastname: Watanabe
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamada
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yagi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamada
authors.forename: Junichi
authors.initials: J
authors.lastname: Kawakami
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000935:Antifungal Agents / Q000097:blood / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D004334:Drug Administration Schedule; D005260:Female; D005919:Glomerular Filtration Rate; D019337:Hematologic Neoplasms / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D016867:Immunocompromised Host; D007160:Immunoproliferative Disorders / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D017964:Itraconazole / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000517:prevention & control*; D012709:Serum Albumin / Q000032:analysis; D012996:Solutions; D053719:Tandem Mass Spectrometry
chemical_list: D000935:Antifungal Agents; D012709:Serum Albumin; D012996:Solutions; D017964:Itraconazole