Pharmacokinetics of recombinant human superoxide dismutase in healthy volunteers

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, inulin or para ‐aminohippurate clearances, or the urinary excretion of β 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. Clinical Pharmacology and Therapeutics (1991) 50 , 713–720; doi: 10.1038/clpt.1991.211