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Thromb Haemost 1992; 67(01): 083-087
DOI: 10.1055/s-0038-1648385
Original Articles
Schattauer GmbH Stuttgart

Liver Blood Flow as a Major Determinant of the Clearance of Recombinant Human Tissue-Type Plasminogen Activator

A de Boer
1   The Centre for Human Drug Research, University Hospital Leiden, The Netherlands
,
C Kluft
2   The Gaubius Laboratory Leiden, The Netherlands
,
J M Kroon
1   The Centre for Human Drug Research, University Hospital Leiden, The Netherlands
,
F J Kasper
1   The Centre for Human Drug Research, University Hospital Leiden, The Netherlands
,
H C Schoemaker
1   The Centre for Human Drug Research, University Hospital Leiden, The Netherlands
,
J Pruis
2   The Gaubius Laboratory Leiden, The Netherlands
,
D D Breimer
3   The Center for Bio-Pharmaceutical Sciences, Division of Pharmacology, University of Leiden, The Netherlands
,
P A Soons
3   The Center for Bio-Pharmaceutical Sciences, Division of Pharmacology, University of Leiden, The Netherlands
,
Jef J Emeis
2   The Gaubius Laboratory Leiden, The Netherlands
,
Adam F Cohen
1   The Centre for Human Drug Research, University Hospital Leiden, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 26 April 1991

Accepted after revision 01 July 1991

Publication Date:
02 July 2018 (online)

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Summary

The influence of changes in liver blood flow on the clearance of rt-PA was studied both in healthy subjects and in a perfused rat liver model. Liver blood flow in healthy subjects was documented indirectly by the clearance of indocyanine green (ICG). Exercise reduced liver blood flow on average by 57% with a 95% confidence interval (95% Cl) ranging from 51% to 62% (n = 5) and increased plasma levels of rt-PA activity (after an i. v. infusion of 18 mg of rt-PA over 120 min) by 119% (95% Cl, 58% - 203%) and rt-PA antigen by 91% (95% Cl, 30% - 140%). In the perfused rat liver model it was shown that halving or doubling of the physiological flow rate of a perfusate, containing rt-PA caused a proportional change in the clearance of rt-PA, while the extraction of rt-PA by the liver remained similar. In conclusion, liver blood flow is a major determinant of the clearance of rt-PA. This may have important implications for dosage of rt-PA in patients with myocardial infarction.

 

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