PAF-induced platelet aggregation ex vivo as a method for monitoring pharmacological activity in healthy volunteers.
Platelet aggregation induced ex vivo by aggregating factors such as adrenaline, ADP, collagen or PAF may be useful as a model for describing drug effects in humans. In the two studies reported here, PAF-induced platelet aggregation ex vivo was used as an indicator of the pharmacological activity in healthy volunteers of the newly developed specific PAF-antagonist WEB 2086. In intravenous and inhalative single rising dose tolerance trials this method proved useful for monitoring the pharmacological action of the compound tested. After administration of placebo no relevant pharmacological activity was observed. In both studies increasing dosages of the test substance showed clear, dose-related inhibition of PAF-induced platelet aggregation. Ex vivo PAF-induced platelet aggregation thus provides a simple and rapid means of assessing functional PAF antagonism during trials of PAF-antagonists in human volunteers.
Adamus
W S
WS
Department of Medicine (Human Pharmacology Centre), Boehringer Ingelheim KG, Ingelheim/Rhein, Federal Republic of Germany.
Heuer
H
H
Meade
C J
CJ
D000328:Adult; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004562:Electrocardiography; D006801:Humans; D008297:Male; D008875:Middle Aged; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011897:Random Allocation; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles
D001381:Azepines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D014227:Triazines; D014230:Triazoles; C052518:WEB 2086