Chen S L, Yang W C, Huang T P, Wann S A, Teng C M
Department of Internal Medicine, Veterans General Hospital Taipei, Taiwan, R.O.C.
Thromb Haemost. 1990 Nov 30;64(3):473-7.
Therapeutic preparations of desmopressin for parenteral use contain the preservative chlorobutanol (5 mg/ml). We show here that chlorobutanol is a potent inhibitor of platelet aggregation and release. It exhibited a significant inhibitory activity toward several aggregation inducers in a concentration- and time-dependent manner. Thromboxane B2 formation, ATP release, and elevation of cytosolic free calcium caused by collagen, ADP, epinephrine, arachidonic acid and thrombin respectively were markedly inhibited by chlorobutanol. Chlorobutanol had no effect on elastase-treated platelets and its antiplatelet effect could be reversed. It is concluded that the antiplatelet effect of chlorobutanol is mainly due to its inhibition on the arachidonic acid pathway but it is unlikely to have a nonspecific toxic effect. This antiplatelet effect of chlorobutanol suggests that desmopressin, when administered for improving hemostasis, should not contain chlorobutanol as a preservative.
用于肠胃外给药的去氨加压素治疗制剂含有防腐剂三氯叔丁醇（5毫克/毫升）。我们在此表明，三氯叔丁醇是血小板聚集和释放的强效抑制剂。它以浓度和时间依赖性方式对几种聚集诱导剂表现出显著的抑制活性。三氯叔丁醇分别显著抑制了由胶原、二磷酸腺苷、肾上腺素、花生四烯酸和凝血酶引起的血栓素B2形成、三磷酸腺苷释放以及胞质游离钙升高。三氯叔丁醇对弹性蛋白酶处理过的血小板没有影响，其抗血小板作用可以逆转。结论是，三氯叔丁醇的抗血小板作用主要归因于其对花生四烯酸途径的抑制，但不太可能具有非特异性毒性作用。三氯叔丁醇的这种抗血小板作用表明，当使用去氨加压素改善止血时，其治疗制剂不应含有三氯叔丁醇作为防腐剂。
