Summary
Pretreatment with 100 mg/kg spironolactone twice daily per os for three days enhances the elimination of i.d. administered 4‴-methyldigoxin in biliary fistula rats, while the absorption of the drug is not affected. The average half life time of total radioactivity in blood is diminished from 9.18 h in control animals to 4.07 h in pretreated rats. This is due to an almost 4 times higher biliary output of radioactivity in pretreated animals. The thin-layer-chromatographic analysis of the biliary and renal excreted radioactivity reveals that apparently, after pretreatment with spironolactone, the O-demethylation, the conjugation reactions and the splitting of glycosidic bonds are increased. However, the enhanced metabolism alone cannot account for the enhanced elimination. Thus the hepatic uptake of the drug is also increased after pretreatment with spironolactone as evidenced by studies on liver slices. The observed increase of bile flow also indicate an alteration of the biliary secretion mechanism under the influence of spironolactone.
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Abshagen, U. Effects of pretreatment with spironolactone on pharmacokinetics of 4‴-methyldigoxin in rats. Naunyn-Schmiedeberg's Arch. Pharmacol. 278, 91–100 (1973). https://doi.org/10.1007/BF00501866
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DOI: https://doi.org/10.1007/BF00501866