Endothelial binding of recombinant tissue plasminogen activator: quantification in vivo using a recirculatory model

J Pharmacokinet Pharmacodyn. 2003 Feb;30(1):3-22. doi: 10.1023/a:1023293325245.


Binding of tissue plasminogen activator (t-PA) to the endothelium may be important in the prevention of thrombus formation. The aim was to develop a method to quantify endothelial binding in vivo. Nine healthy male volunteers received a 40 min continuous infusion with low dose recombinant t-PA (3.75 micrograms/min) and an indocycanine green infusion (0.5 mg/min) as control. A three-compartment recirculatory model was developed to account for non-specific circulatory delay effects. t-PA antigen, activity and t-PA/PAI-1 complex profiles showed a marked delay in increase at the beginning of the infusion. A reversible and concentration-dependent binding component was incorporated in the model which resulted in an accurate description of the t-PA concentration profile. t-PA binding was characterized by a dissociation constant of 5.9 ng/ml (SEM 1.8, CV 0%; fixed) and a binding capacity of 70 micrograms t-PA (SEM 10, CV 48%). This model can be used as a tool to quantify the ability of the endothelium to bind t-PA.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Blood Circulation / drug effects
  • Blood Circulation / physiology
  • Endothelium, Vascular / metabolism*
  • Humans
  • Male
  • Models, Biological*
  • Protein Binding / drug effects
  • Protein Binding / physiology
  • Tissue Plasminogen Activator / blood
  • Tissue Plasminogen Activator / metabolism*
  • Tissue Plasminogen Activator / pharmacology


  • Tissue Plasminogen Activator