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Pharmacokinetics of recombinant human superoxide dismutase in healthy volunteers
Author(s) -
Tsao Cecillia,
Greene Paula,
Odlind Bo,
Brater D Craig
Publication year - 1991
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1991.211
Subject(s) - pharmacokinetics , pharmacology , bolus (digestion) , reabsorption , renal function , excretion , urinary system , chemistry , renal physiology , crossover study , medicine , endocrinology , kidney , placebo , alternative medicine , pathology
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