digoxin and Cholestasis

digoxin has been researched along with Cholestasis* in 3 studies

Other Studies

3 other study(ies) available for digoxin and Cholestasis

ArticleYear
The effect of pancreatic and biliary depletion on the in vivo pharmacokinetics of digoxin in pigs.
    European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2006, Volume: 29, Issue:3-4

    Several transporter systems in the liver and intestine are known to change their expression and function during cholestatic disease states. The objective of the present in vivo study was to investigate the effect of biliary depletion, as a method to mimic cholestasis, on the bioavailability and disposition of digoxin in biliary and pancreatic duct cannulated pigs. The study was divided in two parts. In the first part, a solution of 10 microg/kg digoxin was administered intravenously to the cannulated pigs with intact enterohepatic circulation (Control) and during depletion of the bile and pancreatic juice. In the second part, the same dose of digoxin was administered intraduodenally with intact enterohepatic circulation (Control) and during depletion of either bile or pancreatic juice or both. Biliary depletion decreased the flow of bile and pancreas juice as well as the amount of digoxin appearing in the bile. Deprivation of both bile and pancreas juice significantly increased the bioavailability of digoxin, the plasma AUC after enteral administration increased from 17.6+/-4.2 nmol/lh (Control) to 29.6+/-8.3 nmol/lh (P<0.05). The biliary clearance decreased significantly, from 0.22+/-0.11 l/h/kg (Control) to 0.04+/-0.03 l/h/kg during pancreatic and biliary depletion (P<0.05). There was a significant decrease in elimination half-life (P<0.05) and volume of distribution (P<0.01) during the depletion experiments while the systemic clearance remained unchanged. The results clearly suggest that biliary depletion trigger a short-term downregulation, most likely posttranscriptionally mediated, of a sinusoidal uptake transporter in the liver, possibly a pig ortholog of OATP.

    Topics: Animals; Biological Availability; Cholestasis; Digoxin; Organic Anion Transporters; Swine

2006
Pharmacokinetics of intravenously administered digoxin and histopathological picture in rabbits with experimental bile duct obstruction.
    European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2000, Volume: 11, Issue:3

    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.

    Topics: Animals; Area Under Curve; Cholestasis; Digoxin; Half-Life; Injections, Intravenous; Kidney; Liver; Male; Metabolic Clearance Rate; Rabbits

2000
Influence of induced cholestasis on pharmacokinetics of digoxin and digitoxin in dogs.
    American journal of veterinary research, 1990, Volume: 51, Issue:4

    Dogs with ligated common bile ducts were used to determine effects of cholestasis on pharmacokinetics of digoxin and digitoxin. Forty-three dogs were assigned to: group 1--sham-operated controls (n = 13); group 2--dogs with ligated common bile duct (n = 17); group 3--dogs given phenobarbital for 2 weeks before common bile duct was ligated (n = 11); or group 4--dogs with an induced biliary fistula (n = 2). Digoxin (group A) or digitoxin (group B) was given as single IV injections, and digitalis concentration in plasma was measured by radioimmunoassay. In 18 dogs given digoxin, differences in plasma digoxin concentrations among groups 1A to 3A were not significant (P greater than 0.1). Plasma elimination rate of digoxin was delayed in group 2A. Group-3A dogs had a shortened beta phase half-life (t1/2 (beta] and a decreased distribution volume. In 25 dogs given digitoxin, group-2B dogs maintained a significantly higher plasma digitoxin concentration (P less than 0.01) and had a significantly longer t1/2 (beta] than did dogs in groups 1B and 3B (P less than 0.05). In group-3B dogs, plasma digitoxin concentration was decreased and t1/2 (beta] of digitoxin was shortened. In 10 group-B dogs given 3H-digitoxin (groups 1B, 2B, and 4B), the excretion of total radioactivity in urine and bile was 15 to 20 and 7% of the dose, respectively in the first 24 hours. Most radioactivity in urine and bile was a dichloromethane-unextractable fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

    Topics: Animals; Cholestasis; Digitoxin; Digoxin; Dogs; Female; Ligation; Liver; Male

1990