Free-to-Bound Serum Phenobarbital Levels in Dogs

Abstract

Monitoring phenobarbital levels in dogs has not traditionally taken free-to-bound serum phenobarbital levels into consideration. This study was designed to evaluate free-to-bound phenobarbital in healthy research dogs during the initiation of therapy with phenobarbital. These findings were compared with the levels obtained during routine therapeutic monitoring of phenobarbital in epileptic dogs. This appears to be the first descriptive study which has looked at free-to-bound phenobarbital in clinical canine patients. During the first week of therapy in healthy canine subjects, the free-to-bound ratio was 0.7 due to the high degree of protein-binding of serum phenobarbital. This was in contrast to the level of protein-binding in epileptic patients receiving phenobarbital chronically, with a free-to-bound ratio of 3.0 ± 2.7. Moreover, during the initiation of therapy with phenobarbital, some of the bound fraction could be displaced with sulfadimethoxine indicating that free-to-bound phenobarbital may have significance during this period. On the other hand, chronic therapy in epileptic dogs leads to reduction in the bound fraction for serum phenobarbital. This leads to a strong, direct correlation of total and free phenobarbital in these patients. This relationship is consistent over a wide range of serum concentrations and does not appear to be affected by the age of the patient, the length of chronic therapy or the presence of other anticonvulsant medications. There was an inverse relationship with total plasma proteins and free phenobarbital concentrations, but it was not statistically significant. Routine monitoring of free-to-bound phenobarbital may not be warranted except under specific conditions.