We studied the effect of
nafazatrom on plasma
prostacyclin (PGI2) levels, platelet function, and
thromboxane B2 (TxB2), and 12-hydroxy-eicosatetraenoic
acid (12-HETE) production and clinical improvement in 12 patients with
peripheral vascular disease (PVD) by means of a double-blind crossover trial of placebo, 800 or 1600 mg of
nafazatrom four times daily for 1 week, with intervening 2-week washout periods. Plasma PGI2 levels were measured as
6-keto-PGF1 alpha by radioimmunoassay. Platelet function ex vivo was measured as
collagen and
adenosine diphosphate (
ADP)-induced platelet aggregation, release of
12-HETE and
thromboxane A2 (measured as TxB2), and was determined by high-pressure liquid chromatography (HPLC) and radioimmunoassay, respectively. The plasma
6-keto-PGF1 alpha levels were unaffected by
nafazatrom treatment (p greater than 0.25).
Nafazatrom treatment had no effect on TxB2 production, but significantly altered the production of the platelet
12-HETE (p less than 0.05). There was a significant association between the changes in
12-HETE production and clinical improvement. These results suggest that the mechanism of action of
nafazatrom is in part related to the inhibition of platelet function via the
lipoxygenase pathway, independent of PGI2 stimulation.