Moses A M, Howanitz J, van Gemert M, Miller M
J Clin Invest. 1973 Mar;52(3):535-42. doi: 10.1172/JCI107213.
Normal subjects and patients with antidiuretic hormone (ADH) deficiency were studied to determine the mechanism of the antidiuretic action of clofibrate. Before clofibrate treatment, the patients' ability to concentrate urine with a standardized dehydration procedure correlated with the amount of ADH which was excreted. During clofibrate administration all six patients with ADH deficiency developed an antidiuresis which was like that of ADH, since there was no change in sodium, potassium, total solute, or creatinine excretion. There was a correlation between the patients' ability to concentrate urine during dehydration and the subsequent response to clofibrate, and the excretion of ADH during dehydration correlated with the excretion of ADH on clofibrate therapy. Clofibrate-induced antidiuresis in these patients was partially overcome by ethanol and by water loading. Clofibrate interfered with the ability of patients and subjects to excrete a water load and prevented the water load from inhibiting ADH excretion in the normal subjects. These studies suggested that clofibrate was acting through endogenous ADH and this thesis was supported by the failure of clofibrate to produce an antidiuresis when injected into rats with total ADH deficiency (Brattleboro strain) although an antidiuresis was produced in water-loaded normal rats. When the drug was injected into Brattleboro rats with exogenous ADH, clofibrate either did not alter or it inhibited the action of the ADH. The data demonstrate that clofibrate has a significant ADH-like action. This action appears to be mediated through the release of endogenous ADH.
对正常受试者和抗利尿激素（ADH）缺乏的患者进行了研究，以确定氯贝丁酯的抗利尿作用机制。在氯贝丁酯治疗前，患者通过标准化脱水程序浓缩尿液的能力与排泄的ADH量相关。在给予氯贝丁酯期间，所有6名ADH缺乏的患者都出现了类似ADH的抗利尿作用，因为钠、钾、总溶质或肌酐排泄没有变化。脱水期间患者浓缩尿液的能力与随后对氯贝丁酯的反应之间存在相关性，脱水期间ADH的排泄与氯贝丁酯治疗期间ADH的排泄相关。这些患者中氯贝丁酯诱导的抗利尿作用部分被乙醇和水负荷所克服。氯贝丁酯干扰了患者和受试者排泄水负荷的能力，并阻止水负荷抑制正常受试者的ADH排泄。这些研究表明氯贝丁酯是通过内源性ADH起作用的，这一论点得到了以下事实的支持：当将氯贝丁酯注入完全缺乏ADH的大鼠（布拉特洛维菌株）时，它不会产生抗利尿作用，尽管在水负荷的正常大鼠中会产生抗利尿作用。当将该药物注入具有外源性ADH的布拉特洛维大鼠时，氯贝丁酯要么不改变ADH的作用，要么抑制ADH的作用。数据表明氯贝丁酯具有显著的ADH样作用。这种作用似乎是通过内源性ADH的释放介导的。
