Therapeutic and toxic effects of phenobarbital are related to serum concentrations and not the quantity of drug administered orally. Therapeutic monitoring of serum phenobarbital concentration can be helpful in determining the optimal dose.


Monitoring should be performed:

When steady state blood levels are reached after starting treatment or after changing oral dosage (12 to 15 days in dogs). This provides a baseline to guide further changes in doses according to clinical circumstances.

If seizure frequency increases.

• Every 3 to 6 months to verify that blood concentrations are maintained in the therapeutic range.

• If drug-related side effects are suspected.

• If drugs are added that might interfere with phenobarbital’s pharmacokinetics (corticosteroids, cimetidine, chloramphenicol).


Recommended therapeutic range in dogs is 20 to 35 ug/ml (65-194µmol/l). Most dogs will “respond” (reduction in frequency, intensity and severity of the seizures with minimal side effects) when the serum level of phenobarbital is within this range. However, some dogs might need to be in the upper limit of this range while others might need to be below the lower limit.


This therapeutic range is only an indication of changes required in the oral dosage.


It has been recommended that blood samples for measuring serum concentrations should be taken at the time of ‘trough’ serum phenobarbital concentrations (up to 2 hours before the next dose is due). A study by Levisitski and Trepannier (2000) showed that there was no therapeutically relevant change in serum concentrations during the 12 hour period between phenobarbital doses in 33 epileptic dogs. Analysis of data from over 1400 dogs in the Vetoquinol serum monitoring scheme has confirmed that at oral doses <10mg/kg there was no significant difference between trough and non-trough serum phenobarbital levels on dogs on continuous treatment. At oral doses >10mg/kg a significant difference was seen and in these dogs it is important to be consistent in the timing of blood sampling relative to dose times so that sequential samples can be compared.


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