Effect of phenobarbital pretreatment on digitoxin toxicity and biotransformation in guinea-pigs

Pretreatment with phenobarbital enhanced digitoxin toxicity in guinea-pigs. In both male and female animals the LD50 was reduced by one half as compared to control animals. Plasma and bile concentrations were determined at 15, 30, 60 and 120 min after intraperitoneal administration of 3H digitoxin. Plasma from pretreated guinea-pigs always presented higher concentrations of non-metabolized digitoxin and lower amounts of water soluble metabolites than control animals. If these compounds are less active than the parent drug, the increased toxicity of digitoxin after pretreatment with the enzymatic inducer may be explained by inhibition of detoxication.