title: Amphotericin B transfer to CSF following intravenous administration of liposomal amphotericin B.
abstract: OBJECTIVE
  Although amphotericin B (AmB) and its lipid formulations are used for the treatment of fungal infections of the CNS, the kinetics of AmB in the CSF after intravenous administration of liposomal amphotericin B (LAmB) are not well characterized.
  
  
  METHODS
  From 14 paediatric haemato-oncological patients (aged 0.4-19.5 years, median 7.6 years), we obtained 30 CSF samples by means of routine punctures (performed for intrathecal treatment of the underlying diseases) at different timepoints after the prophylactic intravenous infusion of LAmB (AmBisome, 3 mg/kg/day). Concurrent serum samples were obtained to calculate the transfer rates. An HPLC method was used for AmB detection.
  
  
  RESULTS
  CSF levels of AmB 1-100 h after the intravenous infusion of LAmB were between 10 and 120 ng/mL, except in one case with a level of 529 ng/mL. Concurrent serum levels were about 1000-fold higher, ranging between 3 and 75 μg/mL. CSF levels did not show a clear time-dependent concentration profile, but remained at a steady-state for longer than 48 h after infusion. The transfer rate ranged from 0.02% to 0.92% (median 0.13%) and correlated significantly (r=0.801, P<0.001) with increasing time after infusion.
  
  
  CONCLUSIONS
  After the intravenous administration of LAmB, AmB CSF levels were low, confirming published animal data. CSF levels remained at a steady-state level for longer than 48 h. As indicated by published post mortem data, higher levels in brain tissue, which would be necessary for the successful treatment of CNS infections, might be possible.
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria volker.strenger@medunigraz.at.
authors.forename: Volker
authors.initials: V
authors.lastname: Strenger
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinitzer
authors.affiliation: Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria.
authors.forename: Josef
authors.initials: J
authors.lastname: Donnerer
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Nora
authors.initials: N
authors.lastname: Hofer
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Hans Jürgen
authors.initials: HJ
authors.lastname: Dornbusch
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Wanz
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Markus G
authors.initials: MG
authors.lastname: Seidel
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Sperl
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Herwig
authors.initials: H
authors.lastname: Lackner
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schwinger
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Petra
authors.initials: P
authors.lastname: Sovinz
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Benesch
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Urban
mesh_terms: D000293:Adolescent; D000666:Amphotericin B / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002555:Cerebrospinal Fluid / Q000737:chemistry*; D018890:Chemoprevention / Q000379:methods; D002648:Child; D002675:Child, Preschool; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D008297:Male; D009181:Mycoses / Q000517:prevention & control; D044967:Serum / Q000737:chemistry; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; C068538:liposomal amphotericin B; D000666:Amphotericin B
keywords: AmBisome; HPLC; blood–brain barrier; liposomal amphotericin B; transfer rate