Laboratory studies on the intravenous and subcutaneous administration of PK 10169 in man

Intravenous and subcutaneous administration of PK 10169 in healthy human volunteers were studied utilizing numerous old and new laboratory methods for the monitoring of the effects of this agent. In the intravenous studies, individual groups of 10 healthy volunteers were administered with 2,500-12,500 anti-Xa units (25-125 mg) PK 10169 as a single bolus, and blood samples were drawn at 30 min, 1, 4 and 24 h after the administration of the drug. In the subcutaneous studies, 4,000 anti-Xa units (40 mg) b.i.d. of PK 10169 were administered to a group of 10 healthy individuals for 7 consecutive days, and blood samples were drawn 6 h after each dose. Citrated blood samples collected from both studies were centrifuged, plasma was frozen at -70 degrees C in aliquots, and various laboratory parameters were determined in batches. In the intravenous studies, the global clotting assays (activated partial thromboplastin time and thrombin time) were only prolonged at initial stages of treatment, whereas a marked increase in the antiprotease and antifibrinopeptide A generation activity titer was observed for periods of up to 24 h. In the subcutaneous studies, no significant prolongation of the global clotting assays was noted; however, the anti-Xa levels were significantly increased throughout the study period (7 days). Only a trace of anti-IIa activity was observed. In contrast, a strong antifibrinopeptide A generation activity was observed in all samples which persisted after the discontinuation of PK 10169. These studies suggest that PK 10169 may exert its clinical effects by multiple mechanisms which are only partially assessable by routine laboratory methods.