In vivo metabolism of human tissue-type plasminogen activator.

The turnover of human tissue-type plasminogen activator (t-PA), purified from cell culture fluids and radiolabelled with 125I, was studied in 2 healthy males. After injection, the plasma radioactivity initially disappeared with a half-life of about 3 min, but after 30 min reached a plateau level which persisted for several hours. The radioactive material had then already been converted to forms soluble in 10% trichloroacetic acid (TCA). Surface counting rates indicated a rapid uptake in the liver during the first 10 min after injection, followed by a rapid release from the liver, beginning already at 25 min, which coincided with the appearance of the TCA-soluble radioactive material. After 18 h, about 80% of the injected dose had already been excreted in the urine. We conclude that, in humans, injected t-PA is rapidly cleared from the circulation, mainly by the liver, and within 30 min metabolized to low molecular weight forms which ultimately (within 1 d) appear in the urine.