Differential effect of CGS 13080, a thromboxane synthase inhibitor, in suppressing serum and urine immunoreactive thromboxane B₂ in kidney transplant patients

In this report we describe dose-ranging studies in kidney transplant patients to determine the dose of CGS 13080 that suppress thromboxane during periods of rejection. Formation of TXA₂ was identified by urine immunoreactive TXB₂ (i-TXB₂), which measures both the immediate breakdown product TXB₂ and the major urinary metabolite 2,3-dinor-TXB₂. Serum TXB₂ is a measurement of platelet TXA₂ synthesis. In conclusion, 17 kidney transplant patients received seven days' continuous infusion of the TXA₂ synthase inhibitor CGS 13080 after an increase in urine i-TXB₂ levels. The doses of CGS 13080 varied between 0.04 and 0.50 mg/kg/h, and in all patients serum and urine i-TXB₂ accumulations were inhibited. The highest dose was required to maintain inhibition of the urine i-TXB₂ content. Finally, the lack of an effect of CGS 13080 on bleeding time in these patients contrasts with the elevated bleeding time observed in volunteers after a single oral dose. These data encourage more extensive evaluation of CGS 13080 and thromboxane synthase inhibitors for treating renal transplant patients.