Pharmacokinetics of intravenously administered digoxin and histopathological picture in rabbits with experimental bile duct obstruction.
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 Digoxin was administered intravenously as a single dose of 0.02 mg/kg, and blood samples were withdrawn for up to 24 h. Digoxin concentrations were determined by the FPIA method.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.
Wójcicki
M
M
Department of General and Transplantation Surgery, Pomeranian Academy of Medicine, 70-111, Szczecin, Poland.
Drozdzik
M
M
Sulikowski
T
T
Wójcicki
J
J
Gawrońska-Szklarz
B
B
Zieliński
S
S
Rózewicka
L
L
D000818:Animals; D019540:Area Under Curve; D002779:Cholestasis / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D004077:Digoxin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008657:Metabolic Clearance Rate; D011817:Rabbits
D004077:Digoxin