title: Human pharmacokinetics of intravenous recombinant human Cu/Zn superoxide dismutase.
abstract: OBJECTIVE
  Oxidative stress plays an important role in human disease, but antioxidant therapies are limited. Under physiological conditions superoxide is controlled by the enzyme superoxide dismutase. A recombinant human Cu/Zn superoxide dismutase (rhSOD) might open new therapeutic possibilities.
  
  
  METHODS
  Safety profile and pharmacokinetics in plasma and urine were assessed in an open label phase I study with dose-escalation. 18 healthy male volunteers received a single intravenous 10-minute infusion of 150, 300, or 600 mg rhSOD, respectively (n = 6 per dose group).
  
  
  RESULTS
  rhSOD was well tolerated. Peak plasma concentrations (cmax; mean ± SD) were reached at the end of infusion, with 32.96 ± 10.31, 51.60 ± 8.23, and 103.90 ± 19.02 μg/ ml, respectively. Non-compartmental halflife was 1.06 ± 0.37, 1.59 ± 0.64, and 1.63 ± 0.28 hours. Urinary excretion (10 h) showed dose-dependent relative increases with 11.28 ± 6.46 (7.5%), 54.93 ± 15.25 (18.3%), and 191.81 ± 104.60 mg (32.0%).
  
  
  CONCLUSIONS
  Our results show a good safety profile and predictable pharmacokinetics of rhSOD, suggesting that therapeutic exploratory studies might be safely conducted in humans.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Schaller
authors.forename: Peter
authors.initials: P
authors.lastname: Dittrich
authors.forename: Manuela
authors.initials: M
authors.lastname: Felizeter
authors.forename: Ghazaleh
authors.initials: G
authors.lastname: Gouya
authors.forename: Nicolai
authors.initials: N
authors.lastname: Leuchten
authors.forename: Stylianos
authors.initials: S
authors.lastname: Kapiotis
authors.forename: Brigitta
authors.initials: B
authors.lastname: Vcelar
authors.forename: Karola
authors.initials: K
authors.lastname: Vorauer-Uhl
authors.forename: Michael
authors.initials: M
authors.lastname: Wolzt
mesh_terms: D000328:Adult; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D011994:Recombinant Proteins; D013482:Superoxide Dismutase