Phenobarbitone is the therapeutic agent of choice for management of epileptic seizures in dogs. It is accepted that seizure control and minimisation of side effects correlates best with serum concentrations of phenobarbitone rather than dose administered. Phenobarbitone therapy induces hepatic microsomal enzyme systems resulting in increased drug metabolism and reduced half-life and increased doses are therefore required to maintain serum concentrations. Previous work has shown that variation in serum phenobarbitone concentrations in most dogs receiving phenobarbitone within recommended dose ranges is minimal. Hence, timing of blood sample collection relative to drug administration is not clinically relevant. However, this relationship has not been evaluated in dogs requiring higher doses. The study aim was therefore to assess whether timing of blood sample collection, in relation to drug administration, is clinically relevant at high oral doses of phenobarbitone.

Retrospective analysis of 1515 dogs undergoing monitoring of serum phenobarbitone concentrations as part of the Vétoquinol UK phenobarbitone monitoring voucher scheme was performed. Dogs were divided into two groups: the "trough" group, where the sample was collected within 2-hours prior to the next dose, and the "non trough" group, where the sample was not collected within 2-hours prior to the next dose. Data recorded included weight, total daily phenobarbitone dose and serum phenobarbitone concentration. Comparison of the ratio of serum phenobarbitone concentration to total daily dose was performed, using the unpaired t-test with Welch's correction, between trough and non-trough groups in dogs on a total daily dose of <8mg/kg and >8mg/kg.

The results revealed that at a total daily dose of phenobarbitone of <8mg/kg the ratio of serum concentration to total daily dose for the trough group (n=799) was only 2.7% lower than that of the non-trough group (n=464) (p-value = 0.3029), but at >8mg/kg the trough group (n=166) was significantly lower (17.8%, p=0.01114) than the non-trough group (n=86).

In conclusion significant variation occurs in the serum phenobarbitone concentration within a daily dosing interval in dogs on a total daily dose of >8mg/kg of phenobarbitone, when trough versus non-trough sample times are compared. Consistency in timing of blood sample collection in relation to drug dosing is important when phenobarbitone is used at high oral doses to allow accurate assessment and comparison of serum phenobarbitone levels.

Acknowledgements

We are grateful to Vétoquinol UK for access to the voucher scheme data.