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Pharmacokinetics and systemic effects of tissue‐type plasminogen activator in normal subjects
Author(s) -
Tanswell Paul,
Seifried Erhard,
Su Peter C A F,
Feuerer Werner,
Rijken Dingeman C
Publication year - 1989
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1989.120
Subject(s) - pharmacokinetics , plasminogen activator , fibrinolysis , volume of distribution , pharmacology , fibrinogen , tissue plasminogen activator , fibrin , chemistry , medicine , t plasminogen activator , distribution (mathematics) , endocrinology , immunology , mathematical analysis , mathematics
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 α 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. Clinical Pharmacology and Therapeutics (1989) 46 , 155–162; doi: 10.1038/clpt.1989.120