Improved bioavailability and clinical response in patients with chronic liver disease following the administration of a spironolactone: beta-cyclodextrin complex.
OBJECTIVE
To compare the absorption and clinical effect of spironolactone from an inclusion complex with beta-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, 6beta-hydroxyl 7alpha-thiomethyl spironolactone and 7alpha-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: beta-cyclodextrin complex formulation should lead to a reduction in dosage and perhaps a more consistent effect in patients with chronic liver disease.
Abosehmah-Albidy
A Z
AZ
Pharmacy Practice, School of Pharmacy, University of Bradford, UK.
York
P
P
Wong
V
V
Losowsky
M S
MS
Chrystyn
H
H
D001682:Biological Availability; D002192:Canrenone / Q000097:blood; D002908:Chronic Disease; D018592:Cross-Over Studies; D003505:Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004231:Diuresis / Q000187:drug effects; D004232:Diuretics / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008107:Liver Diseases / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013148:Spironolactone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D014882:Water-Electrolyte Balance / Q000187:drug effects; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D004232:Diuretics; D000451:Mineralocorticoid Receptor Antagonists; D047392:beta-Cyclodextrins; C107482:spironolactone-beta-cyclodextrin complex; D013148:Spironolactone; C046564:7-thiomethylspirolactone; C046565:6-hydroxy-7-thiomethylspirolactone; D002192:Canrenone