title: Pharmacokinetics of sulfobutylether-β-cyclodextrin (SBECD) in subjects on hemodialysis.
abstract: BACKGROUND
  The disposition of sulfobutylether-β-cyclodextrin (SBECD), the solubilizing excipient in intravenous (i.v.) voriconazole, was assessed in seven male subjects with end-stage renal disease on hemodialysis and six subjects with normal renal function.
  
  
  METHODS
  All subjects received twice-daily i.v. voriconazole at the standard voriconazole dose [6 mg/kg (96 mg/kg SBECD) every 12 h (Q12h) on Day 1 followed by 3 mg/kg (48 mg/kg SBECD) Q12h on Days 2-4, with a single i.v. dose on the morning of Day 5]. Subjects were sampled at selected pre-dose trough times, at selected times after infusions and intensively on Day 3 (non-dialysis) and Day 4 (dialysis with high-flux membranes). Compartmental analyses were performed by NONMEM.
  
  
  RESULTS
  SBECD disposition was characterized by a two-compartment model. In renal failure, mean central (V(1)) and peripheral compartment volumes (V(2)) were 9.9 and 6.5 L, respectively. In normal subjects, V(1) and V(2) were 9.6 and 5.2 L, respectively; SBECD clearance (CL) was 130 mL/min. CL in renal failure off-dialysis was 2.6 and 48 mL/min during dialysis; mean half-life decreased from 79 to 5 h during dialysis (normal subjects: 2.1 h).
  
  
  CONCLUSIONS
  Hemodialysis can significantly reduce levels of SBECD in subjects with end-stage renal disease.
authors.affiliation: Infectious Diseases, Pfizer Inc., Collegeville, PA, USA. dluke4@comcast.net
authors.forename: David R
authors.initials: DR
authors.lastname: Luke
authors.forename: Nolan D
authors.initials: ND
authors.lastname: Wood
authors.forename: Konrad E
authors.initials: KE
authors.lastname: Tomaszewski
authors.forename: Bharat
authors.initials: B
authors.lastname: Damle
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016022:Case-Control Studies; D005079:Excipients / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005500:Follow-Up Studies; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy*; D008297:Male; D011379:Prognosis; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006435:Renal Dialysis; D014018:Tissue Distribution; D014230:Triazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D065819:Voriconazole; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000935:Antifungal Agents; D005079:Excipients; D011743:Pyrimidines; D014230:Triazoles; D047392:beta-Cyclodextrins; C093196:SBE4-beta-cyclodextrin; D065819:Voriconazole