Estimation of anti-platelet drugs on human platelet aggregation with a novel whole blood aggregometer by a screen filtration pressure method.
1. The effects of anti-platelet drugs on human whole blood aggregation were evaluated using a novel whole blood aggregometer by a screen filtration pressure (SFP) method. 2. The SFP whole blood aggregometer was found to successfully detect whole blood aggregation induced by ADP, collagen and TRAP by measuring the SFP of blood samples. The platelet aggregation threshold index (PATI), the concentration of agonist required with an inducing pressure rate of 50%, varied time-dependently after collection of blood. High values for ADP and collagen were noted immediately after blood collection, suggesting low aggregation activity of platelets, and gradually increase thereafter. 3. Cilostazol (phosphodiesterase 3 inhibitor), dipyridamole, aspirin and tirofiban all inhibited whole blood aggregation in vitro. Inhibitory effects of cilostazol and dipyridamole, but not tirofiban, were markedly enhanced 6 or 7 fold by long pre-incubation (60 min), compared with short pre-incubation (2 min). Such enhancement was only observed with ADP- and not collagen-induced whole blood aggregation. A similar phenomenon was also observed for aggregation with platelet rich plasma (PRP). Cilostazol inhibition of ADP-induced platelet aggregation was more potent with PRP than whole blood (PATI(200)=3.80+/-0.95 microM for whole blood; 2.04+/-0.61 microM for PRP). Inhibitory effects of dipyridamole were attenuated in PRP without erythrocytes. 4. These results demonstrate that the SFP aggregometer can sensitively detect anti-platelet aggregatory effects of various kinds of drugs. So that it is a useful tool for evaluation of anti-platelet drugs.
Sudo
T
T
Thrombosis and Vascular Research Laboratory, Otsuka Pharmaceutical Co., Ltd., 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan. t_sudo@research.otsuka.co.jp
Ito
H
H
Ozeki
Y
Y
Kimura
Y
Y
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D000077407:Cilostazol; D003094:Collagen / Q000494:pharmacology; D004176:Dipyridamole / Q000494:pharmacology; D005374:Filtration / Q000295:instrumentation / Q000379:methods; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010976:Platelet Count; D010979:Platelet Function Tests / Q000295:instrumentation* / Q000379:methods*; D011312:Pressure; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
D000590:Amino Acid Chloromethyl Ketones; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D014443:Tyrosine; D000244:Adenosine Diphosphate; D004176:Dipyridamole; D006493:Heparin; D003094:Collagen; D000077466:Tirofiban; C040308:phenylalanyl-prolyl-arginine-chloromethyl ketone; D000077407:Cilostazol; D001241:Aspirin