Pharmacokinetics and safety of intravenous recombinant human superoxide dismutase (NK341) in healthy subjects.
Recombinant human superoxide dismutase (rhSOD), NK341, was intravenously administered to healthy male volunteers at doses of 1750-35000 U/kg, and the safety and pharmacokinetic properties were evaluated. There were no abnormal findings attributable to the test drug throughout the study, showing that NK341 was well tolerated in healthy subjects. Tri-exponential elimination of the drug from blood was observed with half-lives of about 20 minutes (alpha phase), 80 minutes (beta phase), and 6 hours (gamma phase). The values of the maximal plasma concentration and the areas under the plasma concentration curves linearly increased with the doses given. On the other hand, the urinary recovery of the drug also increased with the dose, ranging approximately from 3%-45% of the dose. The plasma concentration of the drug measured by an enzyme immunoassay was quite comparable to SOD activity measured by electron spin resonance, suggesting that NK341 was present in blood as the active form of SOD.
Uematsu
T
T
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Nagashima
S
S
Umemura
K
K
Kanamaru
M
M
Nakashima
M
M
D000328:Adult; D004361:Drug Tolerance; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*
D011994:Recombinant Proteins; D013482:Superoxide Dismutase