Pharmacokinetics of intravenously administered digoxin and histopathological picture in rabbits with experimental bile duct obstruction

Eur J Pharm Sci. 2000 Sep;11(3):215-22. doi: 10.1016/s0928-0987(00)00096-8.

Abstract

This study aimed to examine the effect of obstructive cholestasis on the pharmacokinetics of digoxin. Eighteen male rabbits were randomly ascribed to the two study groups: the sham-operated control group and the examined group - with common and cystic bile duct ligations. Digoxin was administered intravenously as a single dose of 0.02 mg/kg, and blood samples were withdrawn for up to 24 h. Digoxin concentrations were determined by the FPIA method. The pharmacokinetic parameters were calculated using a noncompartmental analysis. During the whole observation period the blood serum concentrations of digoxin were statistically higher in animals with obstructive cholestasis versus the controls. A significant increase in the area under the plasma concentration-time curve, decrease in the total body clearance and in the volume of distribution on the 6th day after the bile ducts ligation as compared to the sham-operated controls, were observed. The obtained results suggest an impaired elimination of digoxin in obstructive cholestasis in rabbits.

MeSH terms

  • Animals
  • Area Under Curve
  • Cholestasis / blood
  • Cholestasis / metabolism*
  • Cholestasis / pathology
  • Digoxin / administration & dosage
  • Digoxin / blood
  • Digoxin / pharmacokinetics*
  • Half-Life
  • Injections, Intravenous
  • Kidney / metabolism
  • Kidney / pathology
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Metabolic Clearance Rate
  • Rabbits

Substances

  • Digoxin