Combined effect of Web 2086 (Paf antagonist) and ketoprofen (Nsaid) on Paf-induced ex vivo platelet aggregation in bovine.
The effect of the specific PAF-antagonist WEB 2086, a thieno-triazolo-diazepine, and ketoprofen, a NSAID, was investigated on PAF-induced bovine platelet aggregation measured ex vivo in platelet-rich plasma (PRP). WEB 2086 was infused intravenously over 1 min followed immediately by ketoprofen administration over 1 s (both drugs = 3 mg/kg), in a group of six healthy male Friesian calves. Depending on the PAF concentration, a reversible (10(-8)-10(-9) mol/l) and irreversible (10(-5)-10(-7) mol/l) platelet aggregation was observed. The reversible aggregation was completely blocked by pretreatment of the animal with WEB 2086 and ketoprofen. The inhibitory effects observed during the irreversible aggregation were 47.22%, 54.00% and 88.00% at 10(-5), 10(-6) and 10(-7) mol/l PAF, respectively. Moreover, the aggregation obtained in these condition became reversible. Maximal inhibitory effect of WEB 2086 and ketoprofen on PAF-induced platelet aggregation in calves was observed within 30 min after administration of both drugs. This inhibition persisted even after 24 h and was significantly different from control with P < 0.05. The combined effect of both drugs exceeded the sum of the individual effects (synergism). It was concluded that WEB 2086 and ketoprofen very effectively blocked PAF-induced bovine platelet aggregation in platelet-rich plasma. The study also suggested a synergism between both substances.
Bastos da Silva
M
M
Laboratory for Functional Investigation, University of Liege, Faculty of Veterinary Medicine, Sart Tilman, Belgium.
Herion
F
F
Raskinet
R
R
David
J L
JL
Gustin
P
P
Lekeux
P
P
D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D001381:Azepines / Q000008:administration & dosage / Q000494:pharmacology*; D002417:Cattle / Q000097:blood* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007262:Infusions, Intravenous / Q000379:methods / Q000662:veterinary; D007660:Ketoprofen / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010972:Platelet Activating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001381:Azepines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D014230:Triazoles; C052518:WEB 2086; D007660:Ketoprofen