CLINICAL PHARMACOKINETICS AND DELIVERY OF BOVINE SUPEROXIDE-DISMUTASE

Experimentally, superoxide dismutase (SOD) protects against cytotoxological and histotoxological effects of superoxide anions, which play a fundamental role where inflammatory processes are involved. Currently, only bovine copper containing SOD (Cu-SOD) is available for clinical application in the treatment of patients with various arthritic diseases. The intramuscular route is the principal route to administer usual dosages of bovine Cu-SOD 4 to 32mg, 2 or 3 times weekly, A single dose corresponds to an optimal dose ranging from 30 to 200 mu g/kg, determined from an established dose-response curve. After intramuscular injection of bovine Cu-SOD 8, 16 and 32mg the peak plasma concentration occurs 4 to 8 hours postdose and is 0.05, 0.16 and 0.39 mg/L, respectively. Clinically this metallo-protein is particularly effective for the treatment of inflammation and toxicity resulting from ionising irradiations, ischaemia and tumours. The major advantages of liposomally encapsulated bovine Cu-SOD are its improved pharmacokinetic characteristics, leading to a longer plasma half-life and a slower release of free bovine Cu-SOD. In humans, bovine Cu-SOD (foe or liposomal), although a foreign protein, is well tolerated and produces no acute or delayed toxic effects.