Bioassay of aldosterone antagonists in normal human subjects: a relationship between the level of plasma uric acid before treatment and apparent drug responses.

  title={Bioassay of aldosterone antagonists in normal human subjects: a relationship between the level of plasma uric acid before treatment and apparent drug responses.},
  author={Lawrence E. Ramsay and Paul A. Hessian and Michael Tidd},
  journal={British journal of clinical pharmacology},
  volume={2 3},
The activity of single doses of SC-23992, a new aldosterone antagonist, and spironolactone in reversing the effects of fludrocortisone on urinary electrolyte composition in normal subjects was compared with that of placebo in a double-blind crossover study. 2 SC-23992 (50 mg) and spironolactone (125 mg) each significantly increased sodium excretion and the sodium : potassium (Na/K) ratio, and decreased potassium excretion, when compared with placebo. The response to the two active drugs did not… 
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Antagonism of endogenous mineralocorticoids in normal subjects by prorenoate potassium and spironolactone
SummaryThe pharmacological activity of single oral doses of a new aldosterone antagonist, prorenoate potassium, has been compared with spironolactone and placebo in a balanced double-blind crossover
Quantitative comparison of aldosterone antagonists in normal human subjects: prediction of therapeutic potency.
It is suggested that the human bioassay employed in this study provides quantitative information which should be predictive of the therapeutic potency of aldosterone antagonists and shows excellent agreement with clinical experience where SC8109 was considered to have one tenth the potency of spironolactone.
Bioassay of a new aldosterone antagonist and evaluation of a simple method of quantitative comparison
The renal antimineralocorticoid activity of single oral doses of a new aldosterone antagonist OH OPC(ME)‐K was compared to that of spironolactone in two studies in healthy men and the best estimate of the relative potency was 0.60:1.
Relative potency of prorenoate and spironolactone in normal man
There was evidence for a qualitative difference between spironolactone and prorenoate; the latter significantly more potent in retaining potassium than in increasing sodium excretion, and should prove useful in the evaluation of other aldosterone antagonists.
Spironolactone and potassium canrenoate in normal man
It is suggested that a major part of the renal anti mineralocorticoid activity of spironolactone may be attributable to minor sulfur‐containing metabolites or their precursors having a high renal clearance that affords access to their site of activity via the renal tubular fluid.
Comparison of prorenoate potassium and spironolactone after repeated doses and steady state plasma levels of active metabolites.
Both compounds exhibited directly proportional relationships between daily dose and steady state plasma levels of active metabolites, confirming the limitations of the fludrocortisone model in the evaluation of aldosterone antagonists at steady state.
While the response to frusemide was altered by short‐term changes in dietary sodium and potassium, the difference was less than expected from observations in two populations with customary diets differing in similar manner.
Canrenone--the principal active metabolite of spironolactone?
The results of the two studies seem inconsistent with the view that canrenone alone is responsible for the pharmacological activity of both drugs, and suggest that a significant part of the activity of spironolactone may be attributable to metabolites other than canren one.
Furosemide and bumetanide: A study of responses in normal English and German subjects
The mean pretreatment 24‐hr log10 Na/K ratio in the two treatment periods of the English and German subjects correlated with the mean sodium excretion, potassium excretion and log10Na/K after the two diuretics, thus providing a partial explanation for intersubject and interstudy variation.
The pharmacodynamics of single doses of prorenoate potasssium and spironolactone in fludrocortisone treated normal subjects.
Reductions in urinary potassium excretion were significantly larger after prorenoate potassium than after spironolactone, confirming a qualitative difference in the pharmacological activity of the two drugs which has been reported previously.


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