Manankova N M, Nedel'kina S V, Kozhemiakina N N, Salganik R I
Vopr Med Khim. 1976 Nov-Dec;22(6):740-6.
17alpha-hydroxydeoxycorticosterone and its acetate derivative inhibited the activity of rat liver microsomal enzymes. The inhibitory effect of steroids was not accompanied by induction of the enzyme synthesis, which was characteristic for the other known inhibitors of mixed function oxydases (SKF 525-A, DPEA, MPDK). These properties of the steroids suggested their use for prolongation of the effect of drugs, which are inactivated by microsomal enzymes. The suggestion was tested using hexobarbital as an example. The transformation of hexobarbital in vitro by the rat liver microsomal enzymes was completely inhibited by the equimolar amount of the steroid acetate. Treatment of rats with the steroid acetate almost doubled the life-time of the hexobarbital in rat blood and resulted in the 1.5-fold increase of the sleeping time. The most effective dose of the steroid acetate was 5 mg per 100 g of body weight, the drug being injected 15 min before hexobarbital administration.
17α-羟基脱氧皮质酮及其醋酸酯衍生物可抑制大鼠肝脏微粒体酶的活性。甾体的抑制作用并未伴随酶合成的诱导,而这是其他已知的混合功能氧化酶抑制剂(SKF 525-A、DPEA、MPDK)所具有的特征。这些甾体的特性表明它们可用于延长被微粒体酶灭活的药物的作用时间。以己巴比妥为例对这一设想进行了验证。等摩尔量的甾体醋酸酯可完全抑制大鼠肝脏微粒体酶在体外对己巴比妥的转化。用甾体醋酸酯处理大鼠后,己巴比妥在大鼠血液中的半衰期几乎延长了一倍,睡眠时间增加了1.5倍。甾体醋酸酯的最有效剂量为每100克体重5毫克,在给予己巴比妥前15分钟注射该药物。