Safety, tolerability, and pharmacologic activity of multiple doses of the new platelet activating factor antagonist WEB 2086 in human subjects.
The safety, tolerability, and pharmacologic activity of WEB 2086, a novel, specific platelet activating factor antagonist, were examined in two double-blind, placebo-controlled, within-subject crossover studies. In each study, WEB 2086 (three times 40 mg/day or three times 100 mg/day) was administered for 7 days to 12 healthy volunteers. Pharmacologic activity of the compound was monitored with ex vivo platelet activating factor-induced platelet aggregation. Multiple administration of WEB 2086 resulted in a continuous, almost complete inhibition of this aggregation. Nevertheless, no clinically significant drug-related effects on vital and laboratory parameters or obvious drug-dependent adverse reactions were observed. In conclusion, the performed studies confirmed earlier findings that WEB 2086 was an effective platelet activating factor antagonist in human beings and, furthermore, showed no side effects that would provide objections against further clinical trials with this substance in patients.
Adamus
W S
WS
Department of Medicine, Boehringer Ingelheim KG, Ingelheim am Rhein, Federal Republic of Germany.
Heuer
H
H
Meade
C J
CJ
Brecht
H M
HM
D000328:Adult; D001381:Azepines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects; D011674:Pulse / Q000187:drug effects; D011897:Random Allocation; D012119:Respiration / Q000187:drug effects; D013997:Time Factors; D014227:Triazines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D014230:Triazoles
D001381:Azepines; D010972:Platelet Activating Factor; D014227:Triazines; D014230:Triazoles; C052518:WEB 2086