Phenobarbital
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.
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.
This therapeutic range is only an indication of changes required in the oral dosage. |
| |
| Effects of dose on serum concentrations |
In dogs receiving oral doses of phenobarbital >10mg/kg there was a significant difference between ‘trough’ (up to 2 hours before dose due) and ‘non-trough’ serum phenobarbital concentrations. This effect was not significant in dogs receiving doses <10mg/kg. This finding means that ‘trough’ blood samples are not essential for dogs receiving lower doses of phenobarbital. In dogs receiving doses >10mg/kg it is important to be consistent in the timing of blood sampling relative to dose times so that sequential samples can be compared. |
| |
| Bromide |
Therapeutic and toxic effects of bromide are related to serum concentrations and not the quantity of drug administered orally. Therapeutic monitoring of serum bromide 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 (3 to 6 months in dogs). This
provides a baseline to guide further changes in doses according
to clinical circumstances. |
| • |
If
seizure frequency increases. |
| • |
Every
6 to 12 months to verify that blood concentrations
are maintained
in the therapeutic range. |
| • |
If
drug-related side effects are suspected. |
|
Recommended
oral dosage in dogs is 30 mg/kg once daily. Therapeutic serum concentrations
are 880 to 3000 mg/ml as a solitary agent and 810 to 2400 mg/ml
in combination with phenobarbital.
 |
Guide to
canine idiopathic epilepsy |
ver.090910 |
References
Monteiro R, Anderson TJ, Innocent G, Evans NP, Penderis J (2009) Variations in serum concentration of phenobarbitone in dogs receiving regular twice daily doses in relation to the times of administration. Vet Rec 165, 556-559. - PubMed - |