Pharmacokinetics and biochemical efficacy of pirmagrel, a thromboxane synthase inhibitor, in renal allograft recipients.

The effects of a 48-hour 0.5 mg/kg/hr infusion of the thromboxane synthase inhibitor pirmagrel were studied in 10 renal allograft recipients with cyclosporine nephrotoxicity. Plasma concentrations reached a mean steady-state plasma level of 1798 +/- 481 ng/ml. Biphasic, rapid elimination of pirmagrel was observed with a distribution half-life of 6.7 minutes and a terminal half-life of 73 minutes. Plasma clearance and the volume of distribution of the drug were 300 +/- 87 ml/hr/kg and 497 +/- 232 ml/kg, respectively. The pharmacodynamic effects of pirmagrel were marked by a mean 96% suppression of serum thromboxane B2 (TXB2), which coincided with a suppression of urinary excretion of TXB2, 2,3-dinor-TXB2, and 11-dehydro-TXB2 of 85% +/- 8%, 91% +/- 5%, and 89% +/- 9%, respectively. Urinary excretion of all thromboxane metabolites measured at the end of 1 week after termination of infusion was returned to the baseline. In conclusion, pirmagrel caused effective and sustained suppression of all thromboxane derived metabolites in plasma and urine during continuous infusion in kidney transplant patients receiving cyclosporine.