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Effects of increased liver blood flow on the kinetics and dynamics of recombinant tissue-type plasminogen activator*
- Source :
- Clinical Pharmacology & Therapeutics; November 1996, Vol. 60 Issue: 5 p504-511, 8p
- Publication Year :
- 1996
-
Abstract
- Objective: To investigate the influence of increased liver blood flow on the pharmacokinetics and pharmacodynamics of recombinant tissue-type plasminogen activator (rt-PA) and to study the changes in endogenous urokinase-type plasminogen activator (u-PA).Methods: This open, randomized, crossover trial was carried out in a clinical research unit. Eight healthy, nonsmoking volunteers received linear infusions of 24 mg rt-PA and 92 mg indocyanine green over 160 minutes. Sixty minutes after the infusions were started, the subjects consumed a standardized meal to increase liver blood flow on one occasion and abstained from taking food on the other occasion. Plasma concentrations of indocyanine green, tissue-type plasminogen activator (t-PA) antigen, t-PA activity, total u-PA antigen, plasmin-activatable single-chain u-PA (scu-PA), active two-chain u-PA (tcu-PA), fibrinogen, total fibrin, and fibrinogen/fibrin degradation products (TDP), and α2-antiplasmin were measured.Results: After the consumption of the meal, the area under the curve (AUC) was 35% (95% confidence interval [CI]: 25%, 43%) lower for indocyanine green, 15% (CI: 6%, 24%) lower for t-PA antigen, and 11% (CI: 2%, 19%) lower for t-PA activity compared to the AUC after subjects abstained from food. No changes were observed in fibrinogen, TDP, or α2-antiplasmin concentrations that were attributable to the intake of food. The infusion of rt-PA caused a fivefold increase in the concentration of active tcu-PA and a concomitant decrease in scu-PA concentrations by more than 50%.Conclusions: Increased liver blood flow results in an increase in t-PA clearance. The conversion of the inactive zymogen scu-PA to the active tcu-PA is increased by an infusion of rt-PA, but total u-PA antigen concentrations remain unchanged.
Details
- Language :
- English
- ISSN :
- 00099236 and 15326535
- Volume :
- 60
- Issue :
- 5
- Database :
- Supplemental Index
- Journal :
- Clinical Pharmacology & Therapeutics
- Publication Type :
- Periodical
- Accession number :
- ejs19517947
- Full Text :
- https://doi.org/10.1016/S0009-9236(96)90146-0