Comparison of pharmacokinetics of lanoteplase and alteplase during acute myocardial infarction.
OBJECTIVE
Lanoteplase is a rationally designed variant of tissue plasminogen activator. The aim of this study was to examine the pharmacokinetics and functional activity of a single intravenous bolus dose of lanoteplase with those of a bolus plus two-step infusion of alteplase.


METHODS
Seven-centre substudy of the InTIME-I angiographic trial in patients presenting within 6 hours of onset of suspected acute myocardial infarction.


METHODS
A total of 31 patients (28 males, 3 females) enrolled in this substudy [mean age 59 (range 26 to 76) years].


METHODS
Twenty-three patients randomised to lanoteplase received single bolus doses of 15 kU/kg (n = 5), 30 kU/kg (n = 3), 60 kU/kg (n = 9), or 120 kU/kg (n = 6). Eight patients received alteplase <or=100mg as a bolus followed by a two-stage 90 min infusion. Blood samples were analysed for antigen concentration and plasminogen activator (PA) activity.


RESULTS
The distribution plasma half-life of approximately 35 min for lanoteplase was at least five times longer than that of alteplase. Lanoteplase plasma clearance averaged 3 L/h (50 ml/min), whereas the mean plasma clearance of approximately 24 L/h (400 ml/min) for alteplase approaches hepatic blood flow following acute myocardial infarction. PA activity after lanoteplase 120 kU/kg remained for 6 hours, compared with less than 4 hours after alteplase 100mg.


CONCLUSIONS
The longer antigen and activity half-lives, slower clearance and less complicated administration of lanoteplase compared with alteplase suggest that it may offer advantages for use as a single intravenous bolus to achieve reperfusion after myocardial infarction.
Kostis
John B
JB
Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey, USA.
Dockens
Randy C
RC
Thadani
Udho
U
Bethala
Vasnath
V
Pepine
Carl
C
Leimbach
Wayne
W
Vachharajani
Nimish
N
Raymond
Ralph H
RH
Stouffer
Bruce C
BC
Tay
Lee K
LK
Shyu
Wen Chyi
WC
Liao
Wei-chi
WC
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
D005343:Fibrinolytic Agents; C081981:lanoteplase; D010959:Tissue Plasminogen Activator