Summary
The relative bioavailability of spironolactone from a complex with beta-cyclodextrin has been evaluated. Capsules containing 100 mg micronised spironolactone powder were compared with 100 mg spironolactone beta-cyclodextrin complex in 8 healthy volunteers by a single dose, double blind, crossover pharmacokinetic study. Subjects were randomly allocated to each preparation and crossed over after 2 weeks. Relative bioavailability was assessed by the measurement of serum canrenone concentrations.
The mean relative bioavailability of the spironolactone cyclodextrin complex, compared to the micronised spironolactone powder, was 233%. Statistical analysis (Wilcoxon signed rank test) revealed that this difference was significant with a mean area under the serum concentration time curve of 3.90 and 1.88 mg · h · l−1, for the complex and micronised spironolactone powder, respectively. Four of the volunteer also received a 100 mg spironolactone tablet (Aldactone) under identical conditions.
Pharmacokinetic analysis revealed that the mean relative bioavailability of the spironolactone beta cyclodextrin complex and micronised powder when compared with spironolactone tablets (Aldactone) was 252% and 124%, respectively. There was no change in the canrenone elimination half lives of each subject.
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References
Abshagen U, Besenfelder E, Endele R, Koch K, Neubert B (1979) Kinetics of canerenone after single and multiple doses of spironolactione. Eur J Clin Pharmacol 16: 255–262
Clarke JM, Ramsy LE, Shelton JR, Tidd MJ, Murray S, Palmer RF (1977) Factors influencing comparative bioavailability of spironolactone tablets. J Pharm Sci 66: 1429–1432
Cooks CS (1988) Difference in metabolic profile of potassium canrenoate and spironolactone in the rat: mutagenic metabolites unique to potassium canrenoate. Arch Toxicol 61: 201–212
Dahlof CG, Lundborg P, Persson BA, Regardh CG (1979) Reevaluation of the anti-mineralcorticoid effect of the spironolactone metabolite, canrenone, form plasma concentrations determined by a new high pressure liquid chromoatographic method. Drug Metab Dispos 7: 103–107
Debruéres, B, Brétillon A, Duchêne D (1985) Improvement of solubility and bioavailability of spironolactone by inclusion in β-cyclodextrin. Proc Int Symp Control Rel Bioact Mater 12: 118–119
Gantt CL, Gochman N, Dyniewscz JM (1962) Gastrointestinal absorption of spironolactone. Lancet I: 1130–1131
Gantt CL, Gochman N, Dyniewscz JM (1986) Effect of a detergent on gastrointestinal absorption of a steroid. Lancet I: 486–487
Gochman N, Gantt CL (1962) A fluorimetric method for the determination of a major spironolactone (Aldactone) metabolite in human plasma. J Pharmacol Exp Ther 135: 312–316
Hofman LM, Dutt JE, Deysach LG, Loncin H, Tao L (1974) Comparison of spironolactone tablet dosage forms in healthy humans. J Pharm Sci 63: 1248–1253
Karim A, Zagarella J, Hutshell TC, Chao AY, Baltes BJ (1976) Spironolactone. II. Bioavailability. Clin Pharmacol Ther 19: 170–176
Kojima K, Yamamaoto K, Fujioka H, Kaneko H, (1985) Pharmacokinetics of spironolactone and potassium canrenoate in human. J Pharmacobiol Dyn 8: 161–166
Krause W, Karras J Seifert W (1983) Pharmacokinetics of conrenone after oral administration of spironolactone and intravenous injection of canrenoate K in healthy man. Eur J Clin Pharmacol 25: 449–453
Levy G (1962) Availability of spironolactone given by mouth. Lancet II: 723–724
McInnes GT, Asbury MJ, Ramsay LE, Shelton JR, Harrison IR (1982) Effect of micronization on the bioavailability and pharmacologic activity of spironolactone. J Clin Pharmacol 22: 410–417
Melander A, Danielson K, Schersten B, Thulin T, Wåhlin E (1977) Enhancement by food of canrenone bioavailability from spironolactone. Clin Pharmacol Ther 22: 100–103
Merkus FWHM, Overdiek JWPM, Cilissen J, Zuidema J (1983) Pharmacokinetics of spironolactone after a single dose: Evaluation of the true canrenone serum concentrations during 24 hours. Clin Exp Hypertens A5: 239–248
Overdiek JWPM, Hermens WAJJ, Merkus FWHM (1985a) Determination of the serum concentration of spironolactone and its metabolites by high performance liquid chromatography. J Chromatogr 341: 279–285
Overdiek JWPM, Hermens WAJJ, Merkus FWHM (1985b) New insights into the pharmacokinetics of spironolactone. Clin Pharmacol Ther 38: 469–474
Overdiek JWPM, Merkus FWHM (1986) Influence of food on the bioavailability of spironolactone. Clin Pharmacol Ther 40: 531–536
Overdiek JWPM, Merkus FWHM (1987) The metabolism and biopharmaceutics of spironolactone in man. Drug Metab Drug Interact 5: 273–302
Ramsay L, Asbury M, Shelton J, Harrison I (1977) Spironolactone and canrenoate-K: Relative potency at steady state. Clin Pharmacol Ther 21: 602–609
Seo H, Sunuoka M, Hashimoto T, Fujinaga T, Otagiri M, Uekama K (1983) Enhancement of oral bioavailability of spironolactone by inclusion in cyclodextrin. Chem Pharm Bull 31: 286–291
Uekama K (1985) PHarmaceutical applications of methylated cyclodextrins. Pharm Int 6: 61–65
Varadi A, Feher T, Bodragi L, Koref O (1977) Spironolactone metabolism in normal subjects and in patients with liver cirrhosis. Arzneim Forsch 27: 1617–1620
Vila-Jato JL, Blanco J, Vilar A (1986) Spironolactone/-cyclodextrin complex: oral bioavailability in humans. Acta Pharm Technol 32: 82–85
Von Vergin H, Nuss U, Schwurzlander F, Strubel K, Weigand W, Hitzenberger G (1981) Bioverfügbarkeitsuntersuchung zweier Spironolacton-Preparate. Arzneim Forsch 31: 1498–1503
York P (1983) Solid state properties of powders in the formulation and processing of solid dosage forms. Int J Pharm 14: 1–28
Yusuff NT, York P (1988) Phase solubility of complexes between spironolactone and betacyclodextrin. J Pharm Pharmacol 40: 2P
Yusuff NT, York P, Say B (1989) Interaction studies of cyclodextrin: spironolactone complexes using 13C solid state NMR. J Pharm Pharmacol 41: 63P
Yusuff NT (1990) Studies of cyclodextrin complexes for drug delivery-spironolactone: beta cyclodextrin systems. PhD Thesis, University of Bradford, Bradford
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Yusuff, N.T., York, P., Chrystyn, H. et al. Improved bioavailability from a spironolactone beta-cyclodextrin complex. Eur J Clin Pharmacol 40, 507–511 (1991). https://doi.org/10.1007/BF00315231
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DOI: https://doi.org/10.1007/BF00315231