Inhibition of primary ADP-induced platelet aggregation in normal subjects after administration of nitrofurantoin (furadantin).
The evidence indicating that platelets may play a role in the occurrence of certain thromboembolic phenomena has stimulated a search for inhibitors of platelet function. This report presents data to indicate that nitrofurantoin is a potent inhibitor of primary ADP-induced platelet aggregation. The addition of 10 muM nitrofurantoin to citrated platelet-rich plasma obtained from 12 normal subjects produced a 29+/-6% (2 SD) inhibition of the velocity of platelet aggregation induced by 2 muM ADP. The inhibitory effect of nitrofurantoin demonstrated competitive kinetics in respect to ADP. The intravenous (180 mg) or oral (200 mg) administration of nitrofurantoin produced a serum nitrofurantoin concentration ranging from 2.7 to 23 muM in 28 normal subjects. Platelet-rich plasma obtained from these subjects demonstrated inhibition of the velocity of ADP-induced platelet aggregation that correlated with the log of the serum nitrofurantoin concentration (P < 0.001). Collagen-induced platelet aggregation was also inhibited in a dose-related manner, and the bleeding time was significantly prolonged in the two subjects with the highest serum nitrofurantoin concentration. These studies indicate that nitrofurantoin in vivo inhibits platelet function to a degree that is proportional to the serum nitrofurantoin concentration.
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000284:Administration, Oral; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects*; D002021:Buffers; D003094:Collagen / Q000494:pharmacology; D003864:Depression, Chemical; D005260:Female; D006801:Humans; D007700:Kinetics; D009582:Nitrofurantoin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D011453:Prostaglandins / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology; D013997:Time Factors
D002021:Buffers; D011453:Prostaglandins; D000244:Adenosine Diphosphate; D003094:Collagen; D009582:Nitrofurantoin; D013806:Theophylline; D001241:Aspirin