Cardin J P, Ross M G, Ervin M G, Schaffer A V, Douglas F L, Simke J P
Department of Obstetrics and Gynecology, Harbor-University of California at Los Angeles, Torrance 90509.
Am J Obstet Gynecol. 1990 Oct;163(4 Pt 1):1345-9. doi: 10.1016/0002-9378(90)90717-l.
Pharmacologic inhibition of thromboxane synthetase activity has reversed the clinical manifestations of toxemia in the ovine model. To investigate placental transfer and fetal effects of a selective thromboxane synthetase inhibitor, CGS13080 (Ciba-Geigy, Summit, N.J.) was intravenously infused into eight singleton- or twin-bearing ewes near term. During CGS 13080 infusion (0.1 mg/kg/hr), maternal steady-state CGS 13080 levels of 102 +/- 18 ng/ml were achieved within 30 minutes and maternal serum thromboxane generation decreased significantly (13 +/- 3 to 4 +/- 1 ng/ml). However, fetal serum levels of CGS 13080 were only 4% of peak maternal concentrations and fetal serum thromboxane generation did not change. There was no evidence of change in uterine blood flow, maternal or fetal blood pressure, heart rate, blood gas values, or fetal or maternal metabolites of prostacyclin or prostaglandin E2 during the study. We speculate that CGS 13080 may be efficacious in the treatment of human pregnancy-induced hypertension.
在绵羊模型中，对血栓素合成酶活性进行药理抑制已逆转了毒血症的临床表现。为研究一种选择性血栓素合成酶抑制剂CGS13080（新泽西州萨米特市汽巴 - 嘉基公司生产）的胎盘转运及对胎儿的影响，在妊娠晚期对8只单胎或双胎母羊静脉输注该药物。在输注CGS13080（0.1毫克/千克/小时）期间，30分钟内母体CGS13080达到稳态水平，为102±18纳克/毫升，母体血清血栓素生成显著减少（从13±3降至4±1纳克/毫升）。然而，胎儿血清中CGS13080水平仅为母体峰值浓度的4%，且胎儿血清血栓素生成未发生变化。研究期间，未发现子宫血流量、母体或胎儿血压、心率、血气值，或前列环素或前列腺素E2的母体或胎儿代谢产物有变化。我们推测CGS13080可能对治疗人类妊娠高血压有效。
