Phenobarbital is characterized by a half-life of approximately 54-72 hrs in dogs and similar in cats; variability among animals is likely to be marked. We have measured a half-life as short as 12 hrs; for such patients, steady-state does not really occur. As such, during a 12 hr dosing interval, because little drug is eliminated between doses, drug concentrations will accumulated. “Steady-state” should occur in 3 to 5 drug half-lives, or 150 to 360 hrs (approximately 2 weeks).
The therapeutic range recommended in animals is 15 to 40 mcg/ml, although we recommend that concentrations remain below 35 mcg/ml, and ideally, less than 25 mcg/ml to reduce the risk of hepatotoxicity.
When: Baseline steady-state concentrations can be determined at 14 days. Because Phenobarbital can induce drug metabolism, we recommend another sample at 3 months, particularly for patients whose history includes severe seizures.
Sampling times: For routine monitoring, either a peak (2 hr) or trough (just before the next dose) is reasonable, although we suggest a trough sample such that the lowest concentrations can be determined for the patient and so that concentrations can be compared across time. Also, in some patients, the half-life is short enough that trough concentrations are significantly lower than peak. Peak and trough samples are necessary only for animals in which a half-life less than 20 hrs is suspected such that a shorter dosing interval might be recommended. This might occur in a patient whose liver has been induced to more rapidly metabolize the drug. Remember that any time the dose is changed, you should monitor again at 2 to 4 weeks.
Other considerations: Phenobarbital will shorten the half-life of other drugs, including levetiracetam and zonisamide. Its half-life will be prolonged or shorted by other drugs that target drug metabolizing enzymes. Drugs known to have decrease phenobarbital in our lab have included chloramphenicol and imidazole antifungals.