Fotherby K
Royal Postgraduate Medical School, London, England.
Contraception. 1998 Mar;57(3):183-7. doi: 10.1016/s0010-7824(98)00017-1.
Future studies of the pharmacodynamics of oral contraceptives should encompass interactions between various areas of physiology rather than concentrate on single metabolic processes. Changes in one area of metabolism may affect other areas. Insulin plays a central role in metabolic control and, in addition to profound effects on carbohydrate and lipid metabolism, also affects the hematological system. Insulin has been proposed as a major physiological regulator of plasminogen activator inhibitor, and hyperinsulinemia is associated with increased blood coagulability and decreased fibrinoloysis. There is a close relationship between insulin and triglyceride metabolism, and this may affect factor VII activity in blood. There are many interactions between lipid metabolism and hematological factors. The apoprotein of lipoprotein (a) is structurally similar to plasminogen. Tissue factor pathway inhibitor, a regulator of coagulation, circulates in blood bound to LDL and HDL. Some fatty acids may act as a contact surface for activation of hematological factors. Dietary factors also need to be considered. Changes not only in the quantity but also in the composition of dietary fat influence lipid metabolism and also blood levels of a number of hematological factors. Other aspects of pharmacodynamic studies that require consideration and other factors that affect metabolic interrelationships are discussed.
未来口服避孕药的药效学研究应涵盖生理学各领域之间的相互作用，而非仅专注于单一代谢过程。一个代谢领域的变化可能会影响其他领域。胰岛素在代谢控制中起核心作用，除了对碳水化合物和脂质代谢有深远影响外，还会影响血液系统。胰岛素被认为是纤溶酶原激活物抑制剂的主要生理调节因子，高胰岛素血症与血液凝固性增加和纤维蛋白溶解减少有关。胰岛素与甘油三酯代谢之间存在密切关系，这可能会影响血液中因子VII的活性。脂质代谢与血液学因子之间存在许多相互作用。脂蛋白(a)的载脂蛋白在结构上与纤溶酶原相似。凝血调节因子组织因子途径抑制剂在血液中与低密度脂蛋白和高密度脂蛋白结合循环。一些脂肪酸可能作为激活血液学因子的接触表面。饮食因素也需要考虑。饮食脂肪不仅在数量上而且在组成上的变化都会影响脂质代谢以及许多血液学因子的血液水平。文中还讨论了药效学研究中其他需要考虑的方面以及影响代谢相互关系的其他因素。
