Sullivan M H, Ahmed Y, Elder M G
Institute of Obstetrics and Gynaecology, Royal Postgraduate School, Hammersmith Hospital, London, U.K.
Prostaglandins. 1993 Jul;46(1):21-6. doi: 10.1016/0090-6980(93)90059-g.
It has been proposed that thromboxane synthetase inhibitors may be of use in the treatment of hypertensive disorders of pregnancy. A patient in whom aspirin did not prevent the development of pre-eclampsia in a previous pregnancy was treated with a thromboxane synthetase inhibitor (dazmegrel, Pfizer) in addition to low-dose aspirin. Increased urinary levels of 6-keto-prostaglandin F1 alpha were found throughout pregnancy, which is consistent with the mode of action. At 17-18 weeks of gestation urinary prostaglandin E2 and F2 alpha levels were increased compared with control pregnancies. These increases in PGE2 and PGF2 alpha production were associated with mid-trimester abortion. In vitro studies were carried out to determine the effects of dazmegrel on platelet eicosanoid production. In whole blood from non-pregnant female volunteers this compound inhibited thromboxane B2 production and significantly enhanced prostaglandin E2 production and slightly increased prostacyclin production, demonstrating a redirection of prostaglandin endoperoxides. This suggested that similar changes in arachidonic acid metabolite production may occur in vivo and in vitro, and that thromboxane synthetase inhibitors should not be used during early pregnancy, since increased production of prostaglandins E2 and F2 alpha may result in preterm labour or abortion.
有人提出，血栓素合成酶抑制剂可能可用于治疗妊娠高血压疾病。一名患者在之前的妊娠中使用阿司匹林未能预防子痫前期的发生，此次除低剂量阿司匹林外，还使用了一种血栓素合成酶抑制剂（达美格雷，辉瑞公司）进行治疗。整个孕期均发现尿中6-酮-前列腺素F1α水平升高，这与该药物的作用方式相符。在妊娠17-18周时，与对照妊娠相比，尿中前列腺素E2和F2α水平升高。PGE2和PGF2α生成的这些增加与孕中期流产有关。进行了体外研究以确定达美格雷对血小板类花生酸生成的影响。在非妊娠女性志愿者的全血中，该化合物抑制血栓素B2的生成，并显著增强前列腺素E2的生成，同时使前列环素生成略有增加，表明前列腺素内过氧化物发生了重定向。这表明体内和体外花生四烯酸代谢产物的生成可能会发生类似变化，并且在妊娠早期不应使用血栓素合成酶抑制剂，因为PGE2和PGF2α生成增加可能导致早产或流产。
