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Effects of liver blood flow on the pharmacokinetics of tissue‐type plasminogen activator (alteplase) during thrombolysis in patients with acute myocardial infarction
Author(s) -
Griensven Johannes M. T.,
Koster Rudolph W.,
Burggraaf Jacobus,
Huisman Linda G.,
Kluft Cornelis,
Kroon Ria,
Schoemaker Rik C.,
Cohen Adam F.
Publication year - 1998
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/s0009-9236(98)90119-9
Subject(s) - medicine , indocyanine green , plasminogen activator , fibrinogen , fibrin , myocardial infarction , thrombolysis , t plasminogen activator , blood flow , tissue plasminogen activator , cardiology , gastroenterology , surgery , immunology
Background The removal of recombinant tissue‐type plasminogen activator (rt‐PA; alteplase) by the liver is so rapid that liver blood flow becomes rate determining for its clearance. In patients with myocardial infarction changes in liver blood flow may result from impaired cardiac performance or drug treatment. Objective To estimate the effect of variations in liver blood flow on t‐PA plasma concentrations during thrombolytic therapy. Methods Fifteen patients with acute myocardial infarction were investigated in an open single‐center study at the coronary care unit of University Hospital Leiden. Patients received thrombolytic treatment with 100 mg rt‐PA over 3 hours. Liver blood flow was estimated by indocyanine green clearance and by Doppler echocardiography. Concentrations of t‐PA antigen, t‐PA activity, indocyanine green, α 2 ‐antiplasmin, fibrinogen, and fibrin and fibrinogen degradation products were measured. Results Indocyanine green clearance and clearance of both t‐PA antigen ( r = 0.78; p < 0:01) and t‐PA activity ( r = 0.54; p < 0.05) were significantly related. Significant associations between t‐PA antigen and fibrin and fibrinogen degradation products and between t‐PA antigen and α 2 ‐antiplasmin were also found. Conclusions The liver blood flow of patients with myocardial infarction is inversely correlated with plasma concentrations of t‐PA. In patients with severely impaired liver blood flow and heart failure, high t‐PA plasma concentrations may occur if standard doses are given. This finding could contribute to optimization of the dosage of t‐PA in certain patient groups. Clinical Pharmacology & Therapeutics (1998) 63 , 39–47; doi: