Influence of induced cholestasis on pharmacokinetics of digoxin and digitoxin in dogs

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)