PLATELET-AGGREGATION AFTER NAFTIDROFURYL APPLICATION IN-VITRO AND EX-VIVO

Naftidrofuryl has been shown to inhibit the interaction between platel ets and damaged endothelium, which may lead to thrombosis and is media ted by the 5-hydroxytryptamine. (5-HT2) receptor. This study was desig ned to investigate the effects of naftidrofuryl on 5-HT induced platel et aggregation. In vitro experiments were carried out on platelets fro m healthy laboratory personnel. Naftidrofuryl(0.0625 - 100 mu M) cause d a continual increase in in vitro inhibition, whereby the inhibition at 0.0625 mu M was already significant when compared to control (p < 0 .05). The IC50 was approximately 10 mu M. Ten mu M naftidrofuryl in vi tro caused inhibition of the 5-HT (0.125 - 50 mu M) induced aggregatio n. Subsequently, ex vivo effects of naftidrofuryl on 5-HT induced plat elet aggregation of healthy volunteers together with naftidrofuryl pla sma levels were measured. Twelve healthy volunteers received either 40 0 mg naftidrofuryl or placebo in this double-blind, crossover study. B lood 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 medic ation 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 (V-max) increased from an arbitrary 100% at 8:00 am to about 150% by 10:00 am, remaining at this level un til 5:00 pm. Application of 400 mg naftidrofuryl p.o. resulted in a 50 % decrease in V-max 2 h after drug application. Thereafter, the aggreg ation rose to the initial 100% value 4 h after drug application and re mained at this level during the observation period. Thus, naftidrofury l cancelled the normal circadian increase in aggregation during the mo rning hours and reduced aggregability significantly (p < 0.05) through out the whole observation period in comparison to placebo.