Title
Pharmacokinetics and systemic effects of tissue-type plasminogen activator in normal subjects
Author
Tanswell, P.
Seifried, E.
Su, P.C.A.F.
Feuerer, w.
Rijken, D.C.
Gezondheidsorganisatie TNO Gaubius instituut TNO
Publication year
1989
Abstract
Pharmacokinetics and systemic effects of recombinant tissue-type plasminogen activator (rt-PA) were studied in 18 healthy male volunteers after 30-minute intravenous infusions of placebo, 0.25 mg/kg rt-PA, and 0.5 mg/kg rt-PA. Highly comparable pharmacokinetic parameters were obtained after analysis of rt-PA as both an antigen and an activity. Mean clearance (antigen) was 620 70 (SD) ml/min, volume of distribution at steady state was 8.1 0.8 L, initial volume of distribution was 4.4 0.6 L, and dominant half-life was 4.4 0.3 minutes. The pharmacokinetics of rt-PA were linear, showed low interindividual variation, and are compatible with rapid hepatic elimination of the protein. Systemic plasminogen activation was minimal as assessed by hemostatic assays of plasma samples treated with anti-rt-PA Immunoglobulin G (IgG) to inhibit in vitro fibrinogenolysis. Circulating fibrinogen levels, clotting times, and coagulation factors were unchanged; plasminogen and 2-antiplasmin decreased maximally to 85% and 65% of baseline values, respectively. The data are consistent with the fibrin specificity of t-PA, which is derived from its role in physiologic fibrinolysis.
Subject
Health
Pharmacokinetics
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http://resolver.tudelft.nl/uuid:ab307e15-8a2e-4e96-9882-818a237dd889
DOI
https://doi.org/10.1038/clpt.1989.120
TNO identifier
244061
Source
Clinical pharmacology and therapeutics, 46 (2), 155-162
Bibliographical note
Presented at the Ninth International Congress on Fibrinolysis, Amsterdam, The Netherlands, June 27 through July 1, 1988
Document type
article