Serum concentrations and efficacy of phenytoin, phenobarbital, and primidone in canine epilepsy

Serum concentrations, drug dosages, and seizure control were monitored in 142 dogs on a variety of anticonvulsant treatment regimens, using phenytoin, primidone, and phenobarbital. In 1 of 77 dogs receiving phenytoin, seizures were controlled with a serum concentration of 2.3 micrograms/ml. In 20 of 42 dogs receiving phenobarbital, seizures were controlled with serum concentrations ranging from 14.3 to 43.1 micrograms/ml. In 12 of 23 dogs given primidone, seizures were controlled with similar concentrations of phenobarbital derived from the primidone. Of the dogs in which seizures were uncontrolled by either of these 2 agents, a large proportion had serum phenobarbital concentrations that appeared to be inadequate in spite of what was considered adequate dosage. Further, for dogs given phenobarbital, there was a sixfold variation between dosage and achieved serum concentration, whereas dogs given primidone manifested even greater variability between dosage and serum concentration. This underscores the need for serum concentration monitoring as an adjunct to any drug protocol in seizure control since effectiveness is correlated far better with serum concentrations than with oral dosage. On the basis of these findings, a rational approach to the pharmacologic control of seizures in epileptic dogs was devised.