Effect of picotamide on platelet aggregation and on thromboxane A2 production in vivo.
Effects of picotamide (900 mg in 3 oral administrations for 7 days) on ex vivo and in vivo platelet TxA2 production and on platelet aggregation were evaluated in 8 patients with peripheral arteriopathy and in 8 normal subjects. Picotamide significantly reduced ADP-induced platelet aggregation, but had no effect on that induced by arachidonic acid or the thromboxane analogue U46619. Though ex vivo platelet TxA2 production (TxB2 concentration after arachidonic-acid-induced aggregation) was reduced from 946 +/- 141 (mean +/- SD) to 285 +/- 91 ng/ml in controls and from 1515 +/- 673 to 732 +/- 420 ng/ml in patients with arteriopathy, there was no effect on urinary excretion of 2,3-dinor-TXB2 (in vivo indicator of platelet TxA2 production), or on in vivo PGI2 production (urinary excretion of 6-keto-PGF1 alpha and 2,3-dinor-6-keto-PGF1 alpha). In the same subjects, single-dose aspirin reduced ex vivo TxB2 production by at least 98% and 2,3-dinor-TxB2 excretion from 116.7 +/- 61.4 to 32.6 +/- 17.0 ng/g creatinine in control subjects, and from 156.3 +/- 66.1 to 59.1 +/- 19.2 ng/g creatinine in patients with peripheral arteriopathy. Our data suggest that inhibition of platelet TxA2 production in vivo may not be picotamide's main mechanism of action.
Minuz
P
P
Istituti di Clinica Medica, University of Verona, Italy.
Lechi
C
C
Arosio
E
E
Guzzo
P
P
Zannoni
M
M
Lauciello
C
C
Lechi
A
A
D000368:Aged; D001162:Arteriosclerosis Obliterans / Q000097:blood / Q000652:urine; D011464:Epoprostenol / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D010795:Phthalic Acids / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors; D013928:Thromboxane A2 / Q000096:biosynthesis* / Q000097:blood / Q000652:urine
D010795:Phthalic Acids; D010975:Platelet Aggregation Inhibitors; D013928:Thromboxane A2; C011581:picotamide; D011464:Epoprostenol