Reperfusion half-life: a novel pharmacodynamic measure of thrombolytic activity

We hypothesized that the probability of reperfusion can be modeled by an exponential decay (ie, half-life) function and that this reperfusion half-life is decreased by thrombolytic treatment.

Serial perfusion MRI scans were evaluated for evidence of reperfusion in intravenous tissue plasminogen activator-treated (n=45) and untreated (n=103) patients. The cumulative probability of reperfusion for each group was fit with exponential decay functions. The resulting reperfusion half-life (ie, the time it takes half the sample to reperfuse) was calculated.

In untreated patients, a monoexponential decay function fit the data well (R(2)=0.95) with a half-life of 29.1 hours. In tissue plasminogen activator-treated patients, the data were best fit with a biexponential decay function (R(2)=0.99) that had a fast and a slow component. The fast component is attributable to tissue plasminogen activator therapy and has a half-life of 0.71 hours, whereas the slow component was similar to that of the untreated group. Approximately 3.5 hours after the start of treatment, the effect of tissue plasminogen activator on the probability of reperfusion was negligible.

The probability of reperfusion can be well described by the reperfusion half-life. Determination of the fast component reperfusion half-life may be an approach to compare the relative potency of different thrombolytic agents.