Plasminogen activator response after DDAVP : A clinico-pharmacological study

This study evaluates how plasminogen activator (PA) behaves in response to intravenous (i. v. ) and intranasal (i. n. ) DDAVP in healthy subjects. Five volunteers received in random order four i.v. DDAVP doses (0.1–0.4 μg/Kg) and saline. Changes in PA (euglobulin lysis time) were measured from baseline after 30, 120 and 360 min. PA increased significantly with dose and reached a seven-fold mean rise at 0.4 μg/Kg. Five other subjects, similarly treated with i. n. DDAVP (1–4μg/Kg), showed a significant increase (two-fold over baseline values) but no clear dose-response relationship. To evaluate the rate of PA return to baseline values, seven subjects received a single i.v. DDAVP dose (0.4 μg/Kg) and PA changes were measured at various post-infusion intervals. The pattern of PA clearance from the circulation was clearly bimodal. The mean half-disappearance time of the rapid component was 62 min, that of the slower component, 457 min. Finally, to assess the consistency of PA response following repeated treatment, five healthy subjects were given five daily i.v. doses of DDAVP (0.4 μg/Kg). Even though there was a progressive reduction in the response, a significant increase over baseline was still observed after the last dose.