de Boer A, Kluft C, Kroon J M, Kasper F J, Schoemaker H C, Pruis J, Breimer D D, Soons P A, Emeis J J, Cohen A F
Centre for Human Drug Research, University Hospital Leiden, The Netherlands.
Thromb Haemost. 1992 Jan 23;67(1):83-7.
The influence of changes in liver blood flow on the clearance of rt-PA was studied both in healthy subjects and in a perfused rat liver model. Liver blood flow in healthy subjects was documented indirectly by the clearance of indocyanine green (ICG). Exercise reduced liver blood flow on average by 57% with a 95% confidence interval (95% CI) ranging from 51% to 62% (n = 5) and increased plasma levels of rt-PA activity (after an i.v. infusion of 18 mg of rt-PA over 120 min) by 119% (95% CI, 58%-203%) and rt-PA antigen by 91% (95% CI, 30%-140%). In the perfused rat liver model it was shown that halving or doubling of the physiological flow rate of a perfusate, containing rt-PA caused a proportional change in the clearance of rt-PA, while the extraction of rt-PA by the liver remained similar. In conclusion, liver blood flow is a major determinant of the clearance of rt-PA. This may have important implications for dosage of rt-PA in patients with myocardial infarction.
在健康受试者和灌注大鼠肝脏模型中，研究了肝血流变化对重组组织型纤溶酶原激活剂（rt-PA）清除率的影响。通过吲哚菁绿（ICG）清除率间接记录健康受试者的肝血流。运动使肝血流平均减少57%，95%置信区间（95%CI）为51%至62%（n = 5），并使血浆rt-PA活性水平（静脉输注18 mg rt-PA超过120分钟后）升高119%（95%CI，58%-203%），rt-PA抗原升高91%（95%CI，30%-140%）。在灌注大鼠肝脏模型中，研究表明，含有rt-PA的灌注液生理流速减半或加倍会导致rt-PA清除率成比例变化，而肝脏对rt-PA的摄取保持相似。总之，肝血流是rt-PA清除率的主要决定因素。这可能对心肌梗死患者rt-PA的剂量有重要影响。
