As many Antech clients care for patients that require anticonvulsant therapy, the following summary addresses use of phenobarbital (Phb) and/or bromide (Br), and the laboratory monitoring of therapeutic drug levels.

Phb is the most commonly used anticonvulsant for controlling seizures in dogs, although side-effects may occur especially with long term use.

It is well known that Phb induces increased liver enzymes (SAP, ALT) in most dogs, but rarely does so in cats. Phb can also reduce serum albumin and cholesterol with chronic use, but overt hepatic failure (jaundice, cirrhosis, encephalopathy) is uncommon. The mechanism of hepatic failure is unclear, but is likely a dose- and duration-dependent toxicity. Reducing the dose of Phb will reduce abnormal liver enzyme and/or bile acid levels in most dogs. Bromide treatment may be required in those cases to maintain seizure control.

Phb treatment can alter thyroid and low-dose dexamethasone suppression (LDDS) tests. Phb is associated with decreased total serum T4 and Free T4, but normal T3 and normal or increased TSH concentrations. This may be due to such factors as the increased clearance of T4, increased biliary excretion of T4 as bile flow increases, and increased peripheral deiodination of T4 to T3. Thus, while Phb treatment may mimic hypo-thyroidism biochemically, the patient should not appear clinically hypothyroid, unless there is concomitant hypothyroidism.

Phb also enhances the clearance of dexame-thasone, which may lead to a false positive (escape from suppression) on LDDS testing. However, Phb does not affect the cortisol response to ACTH stimulation or endogenous ACTH concentrations. Therefore, when testing for Cushing’s disease in dogs, receiving Phb, the ACTH stimulation rather than LDDS test should be used. Dogs receiving mitotane (Lysodren®) as well as Phb may require higher loading and maintenance doses of mitotane as Phb increases its elimination.

In rare instances, blood dyscrasias can result from Phb use (eg. thrombocytopenia, neutropenia, anemia). The underlying mechanism is unknown although it could involve deranged folate metabolism (seen with Phb treatment in humans), drug-induced immune-mediated disease, or direct marrow toxicity.

Phb should be given BID (q. 12 hours) in most dogs, and is given or needed TID (q. 8 hours) much less commonly. The elimination half-life is much greater than 12 hours in most dogs, and so levels are well sustained throughout a 12 hour period.

It is commonly recommended to measure serum Phb concentrations at specific times, either just prior to the next dose (trough) or at 4 to 8 hours after dosing (peak). However, recent data indicate that once steady state concentrations have been reached (2 to 3 weeks after beginning treatment or after a dosage alteration), peak and trough Phb concentrations are not significantly different. Thus, in most dogs, only a single sample is required for Phb therapeutic drug monitoring and the timing of sample collection in relationship to dosing has little effect on clinical decisions.

Serum separator gel tubes (SST) should not be used for Phb measurements or for any therapeutic drug monitoring, as the drug absorbs to the gel giving falsely low serum drug concentrations.

The therapeutic range for serum Phb concentrations is 15-45 ug/mL. A recent rise in Phb level without an increase in dose may signal the onset of liver failure, and should be followed up with bile acids testing.

For dogs receiving KBr and Phb, less Phb may be required to control seizures and 20% or more of dogs started on KBr can be taken off Phb altogether.