Premium
Effects of changing liver blood flow by exercise and food on kinetics and dynamics of saruplase
Author(s) -
Griensven Jean M. T.,
Burggraaf Koos J.,
Gerloff Joachim,
Günzler Wolfgang A.,
Beier Horst,
Kroon Ria,
Huisman Linda G. M.,
Schoemaker Rik C.,
Kluft Kees,
Cohen Adam F.
Publication year - 1995
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/0009-9236(95)90206-6
Subject(s) - indocyanine green , plasminogen activator , fibrinogen , medicine , blood flow , crossover study , blood sampling , endocrinology , chemistry , surgery , pathology , alternative medicine , placebo
Objective To investigate the influence of changes in liver blood flow on the pharmacokinetics and pharmacodynamics of single‐chain unglycosylated urokinase‐type plasminogen activator. Methods This open, randomized, crossover trial was carried out in the clinical research unit. Infusions of 37.5 mg saruplase and 90 mg indocyanine green were administered over 150 minutes to 10 healthy male volunteers. After 60 minutes the subjects consumed a standardized meal to increase liver blood flow or performed an exercise test (20 minutes) to decrease liver blood flow. Indocyanine green concentrations, total urokinase‐type plasminogen activator (u‐PA) antigen, two‐chain u‐PA activity, fibrinogen, total degradation products, α 2 ‐antiplasmin, and factor XII‐dependent fibrinolytic activity were measured. Blood flow was measured after food intake in a portal vein branch with Doppler echography. Results The weighted average indocyanine green concentration after exercise was increased by 29% compared with baseline (steady‐state concentration) values (95% confidence intervals [CI]: +6%, +56%). After food, the concentration was 27% lower compared with baseline values (95% CI: −35%, −19%), and portal vein flow was increased by a maximum of 103% (95% CI: +71%, +136%). Average maximal concentrations of u‐PA antigen after exercise were increased by 130 ng/ml compared with baseline concentrations (95% CI: +65, +195 ng/ml) and, unexpectedly, 156 ng/ml higher after food (95% CI: +59, +253 ng/ml). Although not significant, an increase in average u‐PA antigen concentration compared with baseline values was detected after both exercise (7%) and food (13%). This tendency toward a larger effect after food compared with the effect after exercise was reflected by minor changes in the pharmacodynamics. Conclusions u‐PA plasma concentrations were increased by reduced liver blood flow induced by exercise. Food intake produced an unexpected increase in u‐PA concentrations despite increases in liver blood flow. Clinical Pharmacology & Therapeutics (1995) 57 , 381–389; doi: