ISSN:
1432-1041
Keywords:
Spironolactone pharmacokinetics
;
tritiated metabolites
;
fluorigenic metabolites
;
decompensated liver disease
;
enzyme induction
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
Summary Six male patients with histologically characterised, decompensated liver disease who had not previously received spironolactone, were given orally Aldactone® 7 mg/kg with3H-spironolactone 100 µCi. The kinetics of the drug were studied in plasma and urine for 6 days. Then, Aldactone® 7 mg/kg was given daily for 12 consecutive days, and the pharmacokinetics of a single dose of3H-spironolactone were re-examined. The kinetics of total radioactivity, as well as of fluorigenic metabolites in plasma, after the first single dose of spironolactone did not differ in patients and normal test subjects; similar percentages of the dose given were excreted within 6 days in urine from patients (47.47±4.88%) and from controls (53.68±2.04%). The kinetics of CH2Cl2/H2O distribution coefficients of labelled material in plasma and urine, as well as TLC analysis of the CH2Cl2 soluble fraction, revealed no significant differences from controls. After treatment for 12 days with spironolactone, 4 out of 6 patients showed marked acceleration in the rate of elimination of radioactivity from plasma and a corresponding increase in excretion of labelled compounds in urine. Analysis of the excretion products in urine revealed proportionally increased excretion and no evidence of selective induction of a single degradation step. In contrast, delayed elimination was observed in the 2 other patients after 12 days' treatment. However, this was due to dehydration and oliguria caused by over-treatment with the diuretic.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00606406
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