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Improved bioavailability and clinical response in patients with chronic liver disease following the administration of a spironolactone: β‐cyclodextrin complex
Author(s) -
AbosehmahAlbidy A. Z. M.,
York P.,
Wong V.,
Losowsky M. S.,
Chrystyn H.
Publication year - 1997
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.1997.00626.x
Subject(s) - spironolactone , bioavailability , crossover study , medicine , chronic liver disease , pharmacology , liver disease , endocrinology , aldosterone , gastroenterology , cirrhosis , pathology , alternative medicine , placebo
Aims To compare the absorption and clinical effect of spironolactone from an inclusion complex with β‐cyclodextrin (SP‐COMP) to Aldactone tablets (ALD) in chronic liver disease. Methods Patients, admitted with chronic liver disease, completed a randomized crossover steady state study. They received their spironolactone dose as either daily SP‐COMP or ALD for 7 days. Serial blood samples were drawn over a 24 h period from day 7 of each therapy. Accurate fluid balance was recorded on days 5–7 and 12–14. Thirteen (six females) whose mean (s.d.) age and weight was 58.4(9.3) years and 74.3(19.0) kg completed the study. Results The mean (95% confidence limits) relative bioavailability for SP‐COMP (compared with ALD) from steady state serum concentrations of canrenone, 6β‐hydroxyl 7α‐thiomethyl spironolactone and 7α‐thiomethyl spironolactone was 310.0 (265.4, 336.7), 233.4(212.9, 250.8) and 254.8(230.8, 279.0)%, respectively. Improvements in clinical status and fluid balance occurred over the last 3 days of SP‐COMP with a mean (s.d.) net loss, in fluid balance, of 1370(860)ml compared with a gain of 228(936)ml during ALD. Conclusions Better absorption of spironolactone from the spironolactone: β‐cyclodextrin complex formulation should lead to a reduction in dosage and perhaps a more consistent effect in patients with chronic liver disease.