Inhibition of ex-vivo PAF-induced platelet aggregation by the PAF-antagonist RP 48740: relationship to plasma concentrations in healthy volunteers.
RP 48740, 3-(3-pyridyl)-1H,3H-pyrrolo [1,2-c] thiazole-7-carboxamide, a specific competitive PAF-receptor antagonist in vitro, was given to 29 healthy male volunteers for 7 days. Plasma drug concentrations and ex-vivo PAF-induced platelet aggregation were assessed on Days 1, 4, and 7. RP 48740 had linear pharmacokinetics after single and repeated doses. It caused stable inhibition of PAF-induced platelet aggregation in a dose-dependent manner. The effect disappeared within 24 h, even after 7 days of repeated doses. The effect of RP 48740 displayed a sigmoidal relation to the plasma drug concentration; I50 2.3 (0.3) mg.l-1. There were no clinical or biological adverse reactions to RP 48740 during the study.
Pinquier
J L
JL
ECLIMED, Institut de Recherche Thérapeutique, Hôpital Universitaire Cochin, Paris, France.
Sedivy
P
P
Bruno
R
R
Bompart
F
F
Gregoire
J
J
Strauch
G
G
Gaillot
J
J
Clucas
A
A
D000284:Administration, Oral; D000328:Adult; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D012016:Reference Values; D013844:Thiazoles / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*
D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D013844:Thiazoles; C052520:3-(3-pyridinyl)-1H,3H-pyrrolo(1,2-c)thiazole-7-carboxamide