Summary
The plasma concentrations of spirorenone in two groups of male volunteers have been determined after single and 14 daily doses of spirorenone 10 and 40 mg. Independent of the dose and pretreatment, spirorenone was absorbed with a half-life of 20–30 min, achieving maximum concentrations of about 100 ng/ml (10 mg) and 260 ng/ml (40 mg) after 1–2 h. Disposition of the parent drug was biphasic with half-lives of 50–60 min (distribution) and 5–6 h (elimination). Neither significant accumulation nor enzyme induction were observed after prolonged treatment. In one test subject given spirorenone 40 mg, the concentration of an active metabolite, 1,2-dihydrospirorenone, was measured. This compound accumulated considerably after multiple dosing and the area under the plasma concentration-time curve increased from 16 to 52% relative to that of spirorenone itself.
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Bittler D, Hofmeister H, Laurent H, Nickisch K, Nickolson R, Petzoldt K, Wiechert R (1982) Synthesis of spirorenone — a novel highly active aldosterone antagonist. Angew Chem 94: 718; Angew Chem Int Ed Engl 21: 696
Casals-Stenzel J, Brown JJ, Losert W (1981) Pharmacological studies on new steroidal aldosterone antagonists: I. Antialdosterone activity in rats and in healthy man. Naunyn-Schmiedeberg's Arch Pharmacol 316 [Suppl]: R49
Seifert W, Groß Ch, Krais T, Müller U (1982) Pharmacological investigation on the effect of ZK 35973 (spirorenone INN), a new aldosterone antagonist in man. Acta Endocrinol [Suppl] 246, Vol. 99: 94
Krause W, Jakobs U (1982) Determination of plasma levels of spirorenone, a new aldosterone antagonist, and one of its metabolites by high-performance liquid chromatography. J Chromatogr 230: 37
Krause W, Kühne G (1982) Isolation and identification of spirorenone metabolites from the monkey. Steroids 40 [1]: 81
Sutter JL, Lau EPK (1975) Spironolactone. In: Florey K (ed) Analytical profiles of drug substances, Vol.4. Academic Press, New York, p 442
Gantt CL, Gochman N, Dyniewicz JM (1962) Gastrointestinal absorption of spironolactone. Lancet 1: 1130
Shaldon S, Ryder JA, Garsenstein M (1963) A comparison of the use of aldactone and aldactone A in the treatment of hepatic ascites. Gut 4: 16
Bauer G, Rieckmann P, Schaumann W (1962) Einfluß von Teilchengröße und Lösungsvermittlern auf die Resorption von Spironolacton aus dem Magen-Darmtrakt. Arzneimittelforsch 12: 487
Karim A, Zagarella J, Hribar J, Dooley M (1976) Spironolactone I. Disposition and metabolism. Clin Pharmacol Ther 19: 158
Karim A, Zagarella J, Hutsell TC, Dooley M (1976) Spironolactone III. Canrenone-maximum and minimum steady-state plasma levels. Clin Pharmacol Ther 19: 177
Huston GJ, Turner P, Leighton M (1975) Antagonism of fludrocortisone by spironolactone and canrenone. Br J Clin Pharmacol 3: 201
Ramsay L, Shelton JR, Tidd MJ (1976) The pharmacodynamics of single doses of prorenoate potassium and spironolactone in fludrocortisone treated normal subjects. Br J Clin Pharmacol 3: 475
Abshagen U, Rennekamp H, Kuhlmann J (1976) Effects of pretreatment with spironolactone on pharmacokinetics of 4‴-methyldigoxin in man. Naunyn-Schmiedeberg's Arch Pharmacol 292: 87
Taylor S, Rawlins M, Smith S (1972) Spironolactone — a weak enzyme inducer in man. J Pharm Pharmacol 24: 578
Abshagen U, Rennekamp H, Luszpinski G (1977) Disposition kinetics of spironolactone in hepatic failure after single doses and prolonged treatment. Eur J Clin Pharmacol 11: 169
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Krause, W., Sack, C. & Seifert, W. Pharmacokinetics of the new aldosterone antagonist, spirorenone, in healthy volunteers after single and repeated daily doses. Eur J Clin Pharmacol 25, 231–236 (1983). https://doi.org/10.1007/BF00543796
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DOI: https://doi.org/10.1007/BF00543796