Optimizing the bolus/infusion ratio for intravenous administration of urokinase in dogs.
The purpose of this study was to determine the optimal bolus/infusion ratio of urokinase (UK) in a dog model of experimental thrombosis. Radiolabelled clots from dog whole blood were inserted into an extracorporeal jugular loop in anesthetized dogs. Clot size (counts/min) was continuously recorded. UK was administered i.v. as a 1 min bolus (100%/0%), 30 min infusion (0%/100%), or as a bolus/infusion combination at ratios of 75%/25%, 50%/50%, or 25%/75%. The total dose of UK in all groups was 20,000 U/kg. A bolus/infusion ratio of 25%/75% produced twice as much lysis as either bolus or infusion alone. There were no statistical differences between the UK-treated groups in reduction of plasma alpha 2-antiplasmin concentration. We conclude that thrombolytic efficacy was increased by the bolus/infusion administration of UK without a concomitant increase in systemic plasminogen to plasmin conversion.
Klabunde
R E
RE
Department of Pharmacology, Abbott Laboratories, Abbott Park, IL 60064.
Hemenway
C C
CC
Mohrman
S J
SJ
Henkin
J
J
Badylak
S F
SF
D000818:Animals; D004285:Dogs; D004334:Drug Administration Schedule; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008970:Molecular Weight; D013924:Thrombophlebitis / Q000188:drug therapy*; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage* / Q000494:pharmacology; D000979:alpha-2-Antiplasmin / Q000032:analysis
D000979:alpha-2-Antiplasmin; D014568:Urokinase-Type Plasminogen Activator