title: Plasma and cerebrospinal fluid pharmacokinetics of clofarabine in nonhuman primates.
abstract: BACKGROUND
  Clofarabine (2-chloro-2'fluoro-2'-deoxy-9-beta-d-arabinofuranosyladenine) is a purine nucleoside analogue that is active in the treatment of acute leukemia. We studied the pharmacokinetics and cerebrospinal fluid penetration of clofarabine in a nonhuman primate model.
  
  
  METHODS
  A dose of 2.3 mg/kg of clofarabine was given i.v. over 2 hours to each of four animals. Plasma and cerebrospinal fluid (CSF) samples were obtained at specified intervals and the clofarabine concentration determined by reverse-phase high-pressure liquid chromatography with mass spectroscopy.
  
  
  RESULTS
  The median clofarabine clearance was 17 mL/min/kg (range, 15-20), the median plasma area under the concentration-time curve was 452 mumol/L minutes (range, 380-487), and the median terminal half-life was 105 minutes (range, 78-138). Concentrations of clofarabine in CSF could not be modeled reliably because the terminal rate constant was not well defined. The median CSF penetration was 5% (range, 3-26%).
  
  
  CONCLUSIONS
  Clofarabine penetrates into the CSF only modestly, but the concentrations obtained may approach those that are cytotoxic in vitro. Evaluation of the contribution of clofarabine to central nervous system preventive therapy should be considered in future studies.
authors.affiliation: Texas Children's Cancer Center, Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA. sberg@txcc.org
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Berg
authors.forename: Peter L
authors.initials: PL
authors.lastname: Bonate
authors.forename: Jed G
authors.initials: JG
authors.lastname: Nuchtern
authors.forename: Robert
authors.initials: R
authors.lastname: Dauser
authors.forename: Leticia
authors.initials: L
authors.lastname: McGuffey
authors.forename: Bruce
authors.initials: B
authors.lastname: Bernacky
authors.forename: Susan M
authors.initials: SM
authors.lastname: Blaney
mesh_terms: D000227:Adenine Nucleotides; D000818:Animals; D001087:Arabinonucleosides / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D000077866:Clofarabine; D007262:Infusions, Intravenous; D008253:Macaca mulatta; D013058:Mass Spectrometry; D008657:Metabolic Clearance Rate
chemical_list: D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D000077866:Clofarabine