Comparison of fibrinolytic and amidolytic methods for the measurement of streptokinase pharmacokinetics in patients with acute myocardial infarction

Abstract

Plasma samples were obtained from 12 AMI patients administered SK (1.5 × 10 6iu by 1 h infusion) and the plasma levels of SK activity were measured by fibrinolytic and amidolytic assays. Although plasma plasminogen concentrations declined rapidly after the start of infusion there appeared always to be sufficient residual plasmin(ogen) present for activator complex formation. Calibrated fibrinolytic (human fibrin plates) and CNBr-fibrinogen fragment-stimulated amidolytic (S-2251) assays of plasminogen activator activity in euglobulin fractions gave a consistent estimate of SK pharmacokinetics. The peak level of activity (approximately 175 IU/ml plasma) was achieved at the end of the infusion period and activity was cleared with a half-life of approximately 29 min for the majority ( > 80%) of the dose. These values were not affected by the level of pretreatment anti-SK antibody (IgG). It was not possible to quantify SK levels, using bovine fibrin plates because the changing content of human plasminogen in the samples variably affected the lytic response. Measurement of plasma amidolytic activity (when plasmin is inhibited) also did not give a reliable estimate of pharmacokinetics, partly because of interference by plasmin- α 2 macroglobulin complex.