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.
|Number of pages||4|
|Issue number||1 SUPPL. 1|
|State||Published - Jan 1 1988|