title: Platelet aggregation after naftidrofuryl application in vitro and ex vivo.
abstract: 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)
authors.affiliation: Abteilung Klinische Pharmacologie, Universitätsklinikum Frankfurt/M, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Kirsten
authors.forename: B
authors.initials: B
authors.lastname: Erdeg
authors.forename: D
authors.initials: D
authors.lastname: Moxter
authors.forename: K
authors.initials: K
authors.lastname: Hesse
authors.forename: M
authors.initials: M
authors.lastname: Breidert
authors.forename: K
authors.initials: K
authors.lastname: Nelson
mesh_terms: 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
chemical_list: D012702:Serotonin Antagonists; D012701:Serotonin; D009257:Nafronyl