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.