Thromb Haemost 1991; 66(05): 569-574
DOI: 10.1055/s-0038-1646461
Original Article
Schattauer GmbH Stuttgart

Pharmacokinetic and Hemostatic Properties of the Recombinant Plasminogen Activator BM 06.022 in Healthy Volunteers

U Martin
1  The Department of Pharmacology, Boehringer Mannheim GmbH, Mannheim, Germany
,
E von Möllendorff
2  The Department of Clinical Pharmacology, Boehringer Mannheim GmbH, Mannheim, Germany
,
W Akpan
2  The Department of Clinical Pharmacology, Boehringer Mannheim GmbH, Mannheim, Germany
,
R Kientsch-Engel
3  The Diagnostic Research Center, Tutzing, Germany
,
B Kaufmann
2  The Department of Clinical Pharmacology, Boehringer Mannheim GmbH, Mannheim, Germany
,
G Neugebauer
2  The Department of Clinical Pharmacology, Boehringer Mannheim GmbH, Mannheim, Germany
› Author Affiliations
Further Information

Publication History

Received 12 March 1991

Accepted 24 April 1991

Publication Date:
25 July 2018 (online)

Summary

In a randomized, single-blind, placebo-controlled, cross-over Phase-I study pharmacokinetic and hemostatic properties of BM 06.022 were investigated in seven healthy, male human volunteers. The novel recombinant plasminogen activator BM 06.022 consists of the kringle 2 domain and the protease domain of human t-PA and is unglycosylated due to its expression in Escherichia coli cells. Vehicle or 6 MU (= 10.4 mg) BM 06.022 was administered as a single i.v. bolus injection of 10 ml over 2 min. BM 06.022 was well tolerated. Fibrinogen levels and clotting times remained unchanged at baseline levels after 6 MU BM 06.022; plasminogen and α2-antiplasmin (collected on chloromethylketone) decreased maximally to 83 ± 1% and 64 ± 3%, respectively, of baseline. D-dimers and fibrinogen degradation products increased to 1,006 ± 234 ng/ml and 555 ± 155 ng/ml, respectively, after BM 06.022. Half-life of BM 06.022-activity was 11.2 ± 0.4 min and of antigen was 13.9 ± 0.7 min, followed by a terminal half-life only for antigen of 173 ± 33 min. Plasma clearance of BM 06.022 was 371 ± 13 ml/min for activity and 183 ± 15 ml/min for antigen. Thus, BM 06.022 is not fibrinogenolytic at 6 MU and is a fibrinolytic agent with a longer half-life than t-PA.