IMPROVED BIOAVAILABILITY AND CLINICAL-RESPONSE IN PATIENTS WITH CHRONIC LIVER-DISEASE FOLLOWING THE ADMINISTRATION OF A SPIRONOLACTONE - BETA-CYCLODEXTRIN COMPLEX

Aims To compare the absorption and clinical effect of spironolactone f rom an inclusion complex with P-cyclodextrin (SP-COMP) to Aldactone ta blets (ALD) in chronic liver disease. Methods Patients, admitted with chronic liver disease, completed a randomized crossover steady state s tudy. 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 day s 5-7 and 12-14. Thirteen (six females) whose mean (s.d.) age and weig ht 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 canrenon e, 6 beta-hydroxyl 7 alpha-thiomethyl spironolactone and 7 alpha-thiom ethyl 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 a nd 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 spironolac tone from the spironolactone: P-cyclodextrin complex formulation shoul d lead to a reduction in dosage and perhaps a more consistent effect i n patients with chronic liver disease.