Ramsay L E, Hettiarachchi J, Fraser R, Morton J J
Clin Pharmacol Ther. 1980 Apr;27(4):533-43. doi: 10.1038/clpt.1980.75.
Dose-response curves for amiloride and spironolactone were defined in 15 hypertensive patients treated with bendroflumethiazide (bendrofluazide). The relative potency amiloride:spironolactone in correcting hypokalemia was 2.8:1, an estimate significantly lower than the 5:1 potency currently accepted. The relative potency for reduction of plasma sodium was 3.9:1 (amiloride:spironolactone). Amiloride was disproportionately potent in lowering serum bicarbonate, and the data do not suggest that these drugs elevate plasma potassium simply by correcting metabolic alkalosis. Changes in blood pressure were confounded by the presence of carryover effect between treatment phases. Both drugs increased plasma angiotension II and aldosterone, but the rise in aldosterone with spironolactone was smaller than expected from concurrent plasma angiotension II and potassium concentrations. This was consistent with a partial block of aldosterone biosynthesis by spironolactone. The activity of spironolactone did not require the presence of hyperaldosteronism. In a smaller study potassium chloride induced a significant log dose-response on plasma potassium, but the effect was small in absolute terms. At least 64 mmole potassium chloride was needed to match the effect of 20 mg amiloride or 56 mg spironolactone.
在15例接受苄氟噻嗪（苄氟拉嗪）治疗的高血压患者中确定了阿米洛利和螺内酯的剂量反应曲线。阿米洛利与螺内酯纠正低钾血症的相对效价为2.8:1，这一估计值显著低于目前公认的5:1效价。降低血浆钠的相对效价为3.9:1（阿米洛利:螺内酯）。阿米洛利在降低血清碳酸氢盐方面的效力不成比例，并且数据并不表明这些药物仅仅通过纠正代谢性碱中毒来升高血浆钾。治疗阶段之间存在残留效应，使血压变化受到混淆。两种药物均增加血浆血管紧张素II和醛固酮，但螺内酯导致的醛固酮升高幅度小于根据同时存在的血浆血管紧张素II和钾浓度所预期的幅度。这与螺内酯对醛固酮生物合成的部分阻断一致。螺内酯的活性并不需要高醛固酮血症的存在。在一项规模较小的研究中，氯化钾对血浆钾产生了显著的对数剂量反应，但绝对效应较小。至少需要64毫摩尔氯化钾才能与20毫克阿米洛利或56毫克螺内酯的效果相当。
