Changes in metildigoxin pharmacokinetics in cirrhosis of the liver: a comparison with beta-acetyldigoxin.
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| Abstract |
In a prospective randomized study 12 patients suffering from cirrhosis of the liver (stable phase) and 12 healthy volunteers were treated daily with either 0.3 mg metildigoxin (Lanitop) or 0.4 mg beta-acetyldigoxin (Novodigal) orally. Every day the total serum digoxin concentrations of the patients and volunteers were measured by radioimmunoassay. Both digoxin and beta-methyldigoxin are measured by this method. In patients receiving metildigoxin therapy the ratio of beta-methyldigoxin/digoxin in the serum was determined by HPLC. The digoxin levels in patients with cirrhosis treated with metildigoxin were statistically significantly higher than in healthy volunteers. In patients with cirrhosis the proportion of serum beta-methyldigoxin averaged 77.7% of the total digoxin concentration, whereas the proportion was only 37.5% in healthy volunteers. With beta-acetyldigoxin there was no statistically significant difference between patients with cirrhosis and healthy volunteers. The higher total serum-digoxin levels in patients with cirrhosis of the liver after moderate saturation with metildigoxin are caused by reduced demethylation of beta-methyldigoxin to digoxin due to impaired liver function. A comparison with healthy volunteers showed that the reduced hepatic metabolism in the cirrhotic patients caused changes in the pharmacokinetics: a reduced metildigoxin clearance and a smaller distribution volume were found. According to our findings there is more danger of digitalis toxicity in patients with cirrhosis of the liver on a standard dosage of metildigoxin than on a standard dosage of beta-acetyldigoxin.
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| Authors | H Rameis, B Woodcock, J Bonelli, H Waginger |
| Journal | International journal of clinical pharmacology, therapy, and toxicology (Int J Clin Pharmacol Ther Toxicol) Vol. 22 Issue 3 Pg. 145-51 (Mar 1984) ISSN: 0174-4879 [Print] Germany |
| PMID | 6715083 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial) |
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