title: Pharmacokinetics of recombinant human superoxide dismutase in healthy volunteers.
abstract: We studied the pharmacokinetics and effects of recombinant human superoxide dismutase (rhSOD) in 32 normal human volunteers after intravenous bolus doses from 1 mg/kg to 45 mg/kg in a single-blind, placebo-controlled, crossover design. The drug was well tolerated. Neither cardiovascular nor renal function, such as the echocardiographically determined cardiac index, insulin or para-aminohippurate clearance, or the urinary excretion of beta 2-microglobulin or N-acetylglucosaminidase, was affected. Pharmacokinetic analysis by use of noncompartmental methods showed an overall half-life of rhSOD to be about 4 hours for doses from 3 mg/kg to 45 mg/kg. The peak concentrations ranged from 24 to 837 mg/L, and urinary excretion increased from 3% to 57% of total dose after single intravenous bolus administrations of the drug from 1 mg/kg to 45 mg/kg. The mean renal clearance of rhSOD initially increased with dose then plateaued at the highest dose, whereas the nonrenal clearance decreased with dose to a plateau; total clearance remained essentially constant. The progressive increase in renal clearance may be explained by saturation of the tubular reabsorption and degradation of the protein, a mechanism previously described in animal models.
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis.
authors.forename: C
authors.initials: C
authors.lastname: Tsao
authors.forename: P
authors.initials: P
authors.lastname: Greene
authors.forename: B
authors.initials: B
authors.lastname: Odlind
authors.forename: D C
authors.initials: DC
authors.lastname: Brater
mesh_terms: D000328:Adult; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects; D006801:Humans; D007444:Inulin / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology; D012016:Reference Values; D016037:Single-Blind Method; D013482:Superoxide Dismutase / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D011994:Recombinant Proteins; D007444:Inulin; D013482:Superoxide Dismutase