A comparison of the use of Aldactone and Aldactone A in the treatment of hepatic ascites

Abstract

EDITORIAL SYNOPSIS In eight patients with cirrhosis and stable ascites controlled on chlorothiazide and spironolactone, a small particle preparation of spironolactone (Aldactone A) was as effective, at one quarter the dosage, as conventional spironolactone (Aldactone). Plasma spironolactone metabolite levels and urinary excretion of spironolactone metabolite were equivalent with both preparations. The variable dosage requirement of spironolactone in patients with cirrhosis and ascites is discussed in relation to these observations.

Quantitative comparison of aldosterone antagonists in normal human subjects: prediction of therapeutic potency.

“…The best information on the therapeutic potency of SC8109 relative to spironolactone comes from a study comparing the drugs in patients with chronic liver disease where SC8109 had diuretic potency approximately 40% that of spironolactone in the original formulation (Gantt & Dyniewicz, 1959), or 10% that of the formulation used here (Shaldon et al, 1963). Furthermore, in oedematous states (Liddle, 1957(Liddle, , 1958Bolte et al, 1958;Kerr et al, 1958;Slater et al, 1959), primary hyperaldosteronism (Salassa et al, 1958) and essential hypertension (Bolte et al, 1958), the evidence suggests that oral doses of about 1 g of SC8109 were required to produce therapeutic effects comparable to those produced by approximately 100 mg spironolactone in its currently marketed form (Ochs et al, 1978).…”

“…Unfortunately, although active orally, the dosage required was too large to be practicable (Liddle 1957(Liddle , 1958. Clinical evidence suggested a potency ratio of 2.5:1 in favour of spironolactone in its original formulation (Drill, 1962) or 10:1 for the current preparation of spironolactone (Aldactone () which has improved bioavailability (Shaldon, Ryder & Garsenstein, 1963). In this study we used the bioassay developed by Ramsay, Harrison et al (1975) and Ramsay et al (1976) …”

Antagonism of fludrocortisone by spironolactone and canrenone [letter].

“…canrenone failed to improve its efficacy as a mineralocorticoid antagonist. A similar change in physical form increased the activity of spironolactone fourfold (Gantt, Gochman & Dyniewicz, 1962;Shaldon, Ryder & Garsenstein, 1963), further dissociating the activity of spironolactone from canrenone. These results suggest that canrenone is not the principal active metabolite of spironolactone.…”

Oral Absorption with Various Preparations of Spironolactone in Dogs

“…differences in gastrointestinal absorption of various pharmaceutical formulations of spironolactone, as judged by the concentration of its fluorogenic Anmetabolite, aldadiene, in plasma (7)(8)(9) or by renal properties of the preparations (7,8,(10)(11)(12)(13)(14). Noteworthy in these observations is that relatively poor absorption occurred with commercial tablets of spironolactone, which contrasted with the view developed independently from data on mineralocorticoid-blocking properties of the pure drug in the laboratory (2).…”