McInnes G T, Shelton J R, Harrison I R
Clin Pharmacol Ther. 1981 May;29(5):679-86. doi: 10.1038/clpt.1981.95.
The dose ratio approach was used to define the steady-state relative potency of the competitive mineralocorticoid antagonists prorenoate potassium and spironolactone in six healthy male subjects using fludrocortisone as mineralocorticoid agonist. Log fludrocortisone dose-response relationships in the presence or absence of antagonists did not differ from linearity and parallelism, supporting the theoretical basis of the method. Urinary sodium and plasma potassium responses appeared to behave according to the law of mass action, which made possible estimation of the potency of prorenoate relative to spironolactone on a weight basis-4.2:1 (95% C.L. 2.7-6.9:1) and 2.68:1 (95% C.L. 0.71-6.57:1, respectively. The steady-state relative potency for sodium excretion was greater than previously estimated after single doses. Mass action theory could not explain the urinary potassium and log 10 Na/K responses to repeated doses of spironolactone, precluding valid estimation of relative potency for these variables and suggesting that the latter response alone is an unreliable index of overall renal antimineralocorticoid activity.
采用剂量比法，以氟氢可的松作为盐皮质激素激动剂，在6名健康男性受试者中确定竞争性盐皮质激素拮抗剂普乐诺酸钾和螺内酯的稳态相对效价。在有或没有拮抗剂存在的情况下，氟氢可的松的对数剂量-反应关系与线性和平行性无差异，支持该方法的理论基础。尿钠和血钾反应似乎符合质量作用定律，这使得按重量计算普乐诺酸钾相对于螺内酯的效价估计成为可能，分别为4.2:1（95%置信区间2.7 - 6.9:1）和2.68:1（95%置信区间0.71 - 6.57:1）。钠排泄的稳态相对效价比单次给药后先前估计的要高。质量作用理论无法解释重复给予螺内酯后的尿钾和log10 Na/K反应，因此无法有效估计这些变量的相对效价，这表明仅后者的反应是总体肾脏抗盐皮质激素活性的不可靠指标。
