Platelet aggregation after naftidrofuryl application in vitro and ex vivo.
Naftidrofuryl has been shown to inhibit the interaction between platelets and damaged endothelium, which may lead to thrombosis and is mediated by the 5-hydroxytryptamine. (5-HT2) receptor. This study was designed to investigate the effects of naftidrofuryl on 5-HT induced platelet aggregation. In vitro experiments were carried out on platelets from healthy laboratory personnel. Naftidrofuryl (0.0625-100 microM) caused a continual increase in in vitro inhibition, whereby the inhibition at 0.0625 microM was already significant when compared to control (p < 0.05). The IC50 was approximately 10 microM induced aggregation. Subsequently, ex vivo effects of naftidrofuryl on 5-HT induced platelet aggregation of healthy volunteers together with naftidrofuryl plasma levels were measured. Twelve healthy volunteers received either 400 mg naftidrofuryl or placebo in this double-blind, crossover study. Blood samples for determination of aggregation and naftidrofuryl plasma levels were taken before, 0.5, 1, 2, 3, 4, 5, 6.5 and 9 h after medication application. One hour after application of 400 mg naftidrofuryl a maximal plasma level of approximately 380 ng/ml was measured. Under control conditions the aggregation (Vmax) increased from an arbitrary 100% at 8:00 am to about 150% by 10:00 am, remaining at this level until 5:00 pm. Application of 400 mg naftidrofuryl p.o. resulted in a 50% decrease in Vmax 2 h after drug application. Thereafter, the aggregation rose to the initial 100% value 4 h after drug application and remained at this level during the observation period.(ABSTRACT TRUNCATED AT 250 WORDS)
Kirsten
R
R
Abteilung Klinische Pharmacologie, Universitätsklinikum Frankfurt/M, Germany.
Erdeg
B
B
Moxter
D
D
Hesse
K
K
Breidert
M
M
Nelson
K
K
D000328:Adult; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D009257:Nafronyl / Q000097:blood / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology
D012702:Serotonin Antagonists; D012701:Serotonin; D009257:Nafronyl