Chouinard M L, Martin L L, Coffman T, Hamilton B H, Linberg L F, Pamidi A, Simke J P, Rakhit A
Department of Exploratory Clinical Pharmacology, Ciba-Geigy Corporation, Summit, NJ.
Clin Pharmacol Ther. 1992 Dec;52(6):597-604. doi: 10.1038/clpt.1992.197.
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.
在10例患有环孢素肾毒性的肾移植受者中，研究了以0.5毫克/千克/小时的剂量输注血栓素合酶抑制剂吡马格雷48小时的效果。血浆浓度达到了平均稳态血浆水平1798±481纳克/毫升。观察到吡马格雷呈双相、快速消除，分布半衰期为6.7分钟，终末半衰期为73分钟。该药物的血浆清除率和分布容积分别为300±87毫升/小时/千克和497±232毫升/千克。吡马格雷的药效学作用表现为血清血栓素B2（TXB2）平均抑制96%，这与TXB2、2,3 - 二去甲TXB2和11 - 脱氢TXB2的尿排泄抑制分别为85%±8%、91%±5%和89%±9%相吻合。输注结束1周后测定的所有血栓素代谢产物的尿排泄量恢复到基线水平。总之，在接受环孢素的肾移植患者持续输注期间，吡马格雷能有效且持续地抑制血浆和尿液中所有血栓素衍生的代谢产物。
