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Turnover of tPA in rabbits: influence of carbohydrate moieties
1Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892.
Abstract:
The turnover of tissue plasminogen activator (tPA) was studied in rabbits using a double-label technique which allowed the comparison of various tPA derivatives with a standard tPA in individual animals. Purified recombinant tPA (Alteplase) was labelled with 125I and used as a standard for each experiment. Various tPA preparations which lacked specific carbohydrate structures were labelled with 131I (in separate experiments) and injected along with the 125I-tPA standard into rabbits. The clearance of standard tPA was biphasic with an average T 1/2 alpha and T 1/2 beta of 0.85 min and 12 min respectively. Type II tPA which lacks a portion of carbohydrate associated with Type I tPA as well as desialated tPA demonstrated a longer T 1/2 beta than standard tPA.