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Dose‐ranging study of the novel recombinant plasminogen activator BM 06.022 in healthy volunteers
Author(s) -
Martin Ulrich,
Möllendorff Erika,
Akpan Waltraud,
KientschEngel Rosemarie,
Kaufmann Burchard,
Neugebauer Günter
Publication year - 1991
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.1991.160
Subject(s) - plasminogen activator , fibrin , pharmacokinetics , pharmacology , recombinant dna , chemistry , fibrinogen , tissue plasminogen activator , t plasminogen activator , fibrinolysis , medicine , immunology , biochemistry , gene
The novel recombinant plasminogen activator BM 06.022 consists of the kringle 2 and protease domains of human tissue‐type plasminogen activator and is unglycosylated because of its expression in Escherichia coli cells. Pharmacokinetics for activity and hemostatic effects of BM 06.022 were studied in 18 healthy male volunteers after an intravenous bolus injection over 2 minutes. BM 06.022 was administered successively at doses of 0.1125, 0.55, 2.2, 3.3, 4.4, and 5.5 MU to three volunteers. Plasma fibrinogen was unchanged; effects of BM 06.022 were observed on plasminogen only at higher doses, and dose‐dependent effects were seen on α 2 ‐antiplasmin and fibrin D‐dimers. The concentration of plasminogen and α 2 ‐antiplasmin was 87% ± 3% and 79% ± 3%, respectively, of baseline 2 hours after injection of 5.5 MU of BM 06.022. Fibrin D‐dimers were highest with 1147 ± 380 ng/ml at 5.5 MU of BM 06.022. The area under the activity concentration‐time curve (AUC) increased dose‐dependently and linearly. At 5.5 MU of BM 06.022, the AUC was 313 ± 47 IU · hr · ml −1 , the total plasma clearance was 306 ± 40 ml/min, and the half‐life was 14.4 ± 1.1 minutes. Clinical Pharmacology and Therapeutics (1991) 50, 429–436; doi: 10.1038/clpt.1991.160